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Biomedical subjects

H Inouye

Publications and source records attributed to H Inouye.

At least 19 recordsLinked to original sources
PubMed1992

Fibril formation by primate, rodent, and Dutch-hemorrhagic analogues of Alzheimer amyloid beta-protein.

Deposition of extraneuronal fibrils that assemble from the 39-43 residue beta/A4 amyloid protein is one of the earliest histopathological features of Alzheimer's disease. We have used negative-stain electron microscopy, Fourier-transform infrared (FT-IR) spectroscopy, and fiber X-ray diffraction to examine the structure and properties of synthetic peptides corresponding to residues 1-40 of the beta/A4 protein of primate [Pm(1-40); human and monkey], rodent [Ro(1-40); with Arg5-->Gly, Tyr10-->Phe, and His13-->Arg], and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) [Du(1-40); with Glu22-->Gln]. As controls, we examined a reverse primate sequence [Pm*(40-1)] and an extensively substituted primate peptide [C(1-40); with Glu3-->Arg, Arg5-->Glu, Asp7-->Val, His13-->Lys, Lys16-->His, Val18-->Asp, Phe19-->Ser, Phe20-->Tyr, Ser26-->Pro, Ala30-->Val, Ile31-->Ala, Met35-->norLeu, Gly38-->Ile, Val39-->Ala, and Val40-->Gly]. The assembly of these peptides was studied to understand the relationship between species-dependent amyloid formation and beta/A4 sequence and the effect of a naturally occurring point mutation of fibrillogenesis. The three N-terminal amino acid differences between Pm(1-40) and Ro(1-40) had virtually no effect on the morphology or organization of the fibrils formed by these peptides, indicating that the lack of amyloid deposits in rodent brain is not due directly to specific changes in its beta/A4 sequence. beta-Sheet and fibril formation, judged by FT-IR, was maximal within the pH range 5-8 for Pm(1-40), pH 5-10.5 for Du(1-40), and pH 2.5-8 for Ro(1-40).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Role of adrenal and gonadal androgens in insulin action and metabolism.

In a previous report we found extreme hyperinsulinemia associated with high testosterone levels in patients with polycystic ovarian syndrome (PCO) and normal insulin levels in a small group of patients with elevated dehydroepiandrosterone (DHEA). From these observations, we hypothesized that DHEA and testosterone may have opposing actions on insulin sensitivity. To test this hypothesis, we studied insulin sensitivity in vivo and in vitro in a) obese PCO women with elevated testosterone, b) obese patients with adult-onset adrenal hyperplasia (AH) and high levels of DHEA, c) weight-matched obese controls, and d) lean controls. Insulin sensitivity was determined by insulin responses to a standard OGTT, hypoglycemic responses to an IV insulin tolerance test (ITT), red blood cell (RBC) insulin binding and receptor kinase activity, and phytohemagglutinin (PHA)-activated T-lymphocyte (T-cell) insulin binding and PDH insulin sensitivity. In PCO patients, we found that basal and glucose-challenged insulin levels were significantly greater than, and hypoglycemic responses to IV insulin, significantly lower than, weight-matched control values. However, AH patients had insulin values significantly below, and hypoglycemic responses significantly above, those of the weight-matched controls. Their values were, in fact, comparable to those observed for the lean control subjects. Similar findings were observed with insulin binding and PDH insulin sensitivity. Insulin sensitivity in all study subjects was found to be negatively correlated to testosterone and positively correlated to DHEA and, more significantly, to the ratio of DHEA/testosterone. These data would suggest that, in females, DHEA and T may have opposing actions on insulin sensitivity. We conclude that in females insulin sensitivity in vivo and in vitro is modulated, at least in part, by the ratios of DHEA to testosterone.

Adrenal Glands↗
PubMed1991

Folding and function of the myelin proteins from primary sequence data.

To explain how the myelin proteins are involved in the organization and function of the myelin sheath requires knowing their molecular structures. Except for P2 basic protein of PNS myelin, however, their structures are not yet known. As an aid to predicting their molecular folding and possible functions, we have developed a FORTRAN program to analyze the primary sequence data for proteins, and have applied this to the myelin proteins in particular. In this program, propensities for the secondary structure conformations as well as physical-chemical parameters are assigned to the amino acids and the pattern of these parameters is examined by calculating their average values, autocorrelation functions and Fourier transforms. To compare two proteins, their sequences are aligned using a unitary scoring matrix, and homologies are searched by plotting a two-dimensional map of the correlation coefficients. Comparison of the corresponding myelin basic proteins (MBP) and P0 glycoproteins (P0) for rodent and shark showed that the conserved residues included most of the amino acids which were predicted to form the alpha or beta conformations, while the altered residues were mainly in the hydrophilic and turn or coil regions. In both rodent and shark the putative extracellular domain of P0 glycoprotein displayed consecutive peaks of beta propensity similar to that for the immunoglobulins, while the cytoplasmic domain showed alpha-beta-alpha folding. To trace the immunoglobulin fold along the P0 sequence, we compared the beta propensity curve of P0 with that of the immunoglobulin M603, whose three-dimensional structure has been determined. We propose that the flat beta-sheets of P0 are orientated parallel to the membrane surface to facilitate their homotypic interaction in the extracellular space. An extra beta-fold in the extracellular domain of shark P0 compared with rodent P0 was found, and this may result in a greater attraction between the apposed extracellular surfaces and may account for a smaller extracellular space as measured by x-ray diffraction. A computer search of the myelin protein sequences for functional motifs revealed sites for N-glycosylation, phosphorylation, nucleotide binding, and certain enzyme activities. We note especially that there are potential nucleotide binding sites in proteolipid protein (PLP), MBP and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). This is consistent with the experimental observations that PLP acts like an ionophore or proton channel when reconstituted into planar lipid bilayers, MBP binds GTP, and CNP catalyzes in vitro the hydrolysis of 2',3'-nucleotides into corresponding 2'-nucleotides.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1991

Morphology and antibody recognition of synthetic beta-amyloid peptides.

To elucidate the relationship between amyloid fibril formation in Alzheimer disease (AD) and the primary structure of the beta-amyloid protein (beta-AP), we investigated the ability of peptides sharing sequences with beta-AP to form fibrils in vitro and to recognize anti-beta-amyloid antisera. The peptides, which were synthesized using a FMOC solid phase procedure and purified by HPLC, consisted of residues 6-25 from the putative aqueous domain, residues 22-35, which overlaps the putative aqueous and transmembrane domains, and residues 1-38 and 1-40 representing nearly the full length of beta-AP. Electron microscopy of negative-stained or thin-sectioned preparations revealed that the peptides assembled into fibrils having different morphologies, some of which resembled in situ AD amyloid. Peptide 6-25 fibrils had diameters of 50-80 A and occasionally showed a central groove suggestive of constituent filaments. Cross sections of the fibril showed a penta- or hexameric arrangement of globular subunits with diameters of 25-30 A. Peptide 22-35 fibrils were helical, with a pitch of 1,100 A and a width of 120 A at its greatest and 50-60 A at its narrowest. The fibrils formed by peptides 1-38 and 1-40 were 70-90 A in diameter. When the peptide assemblies were singly oriented by sedimentation or doubly oriented in a magnetic field, their X-ray diffraction patterns all showed reflections typical of a cross-beta pleated sheet conformation. The patterns differed mainly in their small-angle equatorial intensity, which arises from the packing of fibrils having different widths. Antiserum raised to either native amyloid or to synthetic peptide beta-(1-28) was highly reactive in an inhibition-ELISA assay to beta-(6-25) and beta-(1-38), but not to beta-(22-35), and immunostained beta-(1-40) on Western blots. These studies show that the beta-(6-25), beta-(1-38) and beta-(1-40) peptides can assemble into cross-beta fibrils that retain epitopes characteristic of AD amyloid.

Amino Acid Sequence↗
PubMed1991

[Enzyme-linked immunosorbent assay using monoclonal antibodies for direct serotyping of enteric adenoviruses in feces].

We were prepared three monoclonal antibodies in which the monoclone 12D was type specific for Adenovirus 40 (Ad40), 1F was type specific for Ad41 and 15D was group specific for Ads. For identification of enteric adenoviruses (EAd) in stool specimens, enzyme-linked immunosorbent assay (ELISA) test using monoclonal antibodies was developed. Results of identification by the ELISA tests using monoclonal antibodies to EAd on 15 fecal samples in which Ad particles were found by electron microscopy showed complete coincidence to those of Sma 1 restriction endonuclease cleavage. From these results, the ELISA tests employing EAds type specific monoclonal antibodies proved to be specific and this was a rapid technique for laboratory diagnosis of EAd in fecal specimens of viral gastroenteritis. Fifty-eight fecal samples with Ad particles positive by EM were serotyped by the ELISA using monoclonal antibodies. Eleven fecal samples were identified as Ad40, 25 as Ad41, 1 as double infection with Ad40 and Ad41, and 4 as non-EAd. These results indicated that Ad41 was more dominant than Ad40 during April, 1986 to January, 1989 in Matsuyama city.

Adenoviruses, Human↗
PubMed1991

Helicobacter pylori is not a co-carcinogen in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric carcinogenesis.

Helicobacter pylori was implicated in gastric carcinogenesis through the induction of metaplasia of the gastric mucosa. In this experiment a co-carcinogenic effect of H. pylori on chemically induced gastric carcinogenesis was examined. Wistar WKY male rats received drinking water containing 50 mg/l of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and intragastric administration of 10(6) to 10(8) colony forming unit of H. pylori thrice a week for 40 weeks. Thus, 3 groups were assigned as Group I; MNNG alone, Group II; MNNG + vehicle, and Group III; MNNG + H. pylori (n = 30, each). At autopsy, 9 rats (30%) had 7 glandular stomach and 3 duodenal tumors in Group I, and 10 rats (33%) had 8 glandular stomach and 2 duodenal tumors in Group II, whereas in Group III 4 rats (13%) had 2 glandular stomach and 2 duodenal tumors (chi 2 = 4.257, P < 0.15 for the incidences of glandular stomach tumors among 3 groups). The finding seems to suggest that H. pylori has an ambitendency in the gastritis-metaplasia-carcinogenesis sequence as a promoter for the induction of the predisposing mucosa and as an inhibitor against certain carcinogens.

Animals↗
PubMed1990

The primary structure and analysis of the squid kinesin heavy chain.

We report the cDNA sequence of the squid kinesin heavy chain and compared the predicted amino acid sequence with that of the Drosophila heavy chain as reported by Yang, J.T., Laymon, R.A., and Goldstein, L.S. B. (1989) Cell 56, 879-889). We compared the two kinesin sequences with regard to the predicted physicochemical parameters of hydrophobicity, charge, and propensities of the secondary conformations. A comparison of the sequences from the two species reveals the head, stalk, and tail domains because a reduced degree of conservation demarcates the stalk. The charge profile indicates that the head region is nearly neutral, the stalk region acidic, and the tail is basic. The Fourier transform analysis of the hydrophobic profile of the stalk shows predominant peaks at 1/3.5 and 1/2.3, which are indexed as the second and third orders of the period 7 residue. As in the Drosophila sequence, the rod domain is divided into an amino and a carboxyl subdomain by a predicted hinge region. We show that the disposition of hydrophobic residues is distinct in these two subdomains. In particular, the heptad repeat is more regular in the amino-terminal rod domain than in the carboxyl-terminal rod domain. The tail region is positively charged, a feature that is consistent with the known electrostatic interaction between the heavy chain and negatively charged surfaces such as glass coverslips and latex beads. Three monoclonal antibodies to the kinesin heavy chain have been mapped to a region within the carboxyl terminus of the stalk.

Adenosine Triphosphatases↗
PubMed1990

Risk assessment of drinking water in a reservoir contaminated by PAH's originated from road traffic.

The loads of Polycyclic Aromatic Hydrocarbons (PAHs) originating from road traffic were measured and in units of per vehicle per meter was estimated as follows: 0.07 ng/veh.m for Benzo[a]pyrene, and 0.83 ng/veh.m for Dibenzanthracene and so on, and 5.77 ng/veh.m for total PAHs. This unit is applied to risk estimation of drinking water in a reservoir where it is planned to construct a new high way the near future, and the concentration in the reservoir water is estimated to be 3.3-101 ng/l for individual PAH's. Assuming standard oral exposure to PAHs in raw water for drinking water supply, the estimated lifetime risk of carcinogenesis was less than 1 in 10(6), which is not considered significant.

Benz(a)Anthracenes↗
PubMed1989

Immunogenetic heterogeneity in type 1 (insulin-dependent) diabetes among Japanese HLA antigens and organ-specific autoantibodies.

HLA phenotypes and haplotypes in relation to organ-specific autoantibody responses were studied in 82 Japanese patients with Type 1 (insulin-dependent) diabetes. HLA-DRw9 antigen and HLA phenotype of DRw9/X (X:not DR4) were increased in patients with organ-specific autoantibodies other than islet cell antibody (CP less than 0.02, RR = 4.02 and p less than 0.05 RR = 2.30, respectively); whereas HLA-DR4 antigen and HLA phenotype of DR4/X (X: not DRw9) were increased in those without the autoantibodies (CP less than 0.001, RR = 3.95 and p less than 0.01, RR = 2.46, respectively). HLA haplotype of Bw61-DRw9 was increased in patients with the autoantibodies (p less than 0.005, RR = 4.94), and HLA haplotype of Bw54-DR4 was increased in those without the autoantibodies (p less than 0.001, RR = 5.52). The relative risk of HLA-DR4/DRw9 was the highest among all HLA-DR phenotypes or genotypes in patients either with or without the autoantibodies. No association was, however, found between the incidence of islet cell antibody and HLA-DR phenotypes. These findings suggest that Type 1 diabetes among Japanese is immunogenetically heterogeneous as is Type 1 diabetes among Caucasians; and the differences in HLA-association of Type 1 diabetes among ethnic groups might give a clue to understanding of a role of HLA-antigens in the development of Type 1 diabetes.

Autoantibodies↗
PubMed1989

Campylobacter pylori in Japan: bacteriological feature and prevalence in healthy subjects and patients with gastroduodenal disorders.

The presence of Campylobacter pylori was investigated in biopsy specimens obtained during gastrofiberscopy from 103 consecutive patients prospectively. Patients included 25 with gastric ulcer, 4 with duodenal ulcer, 5 with coexisting gastroduodenal ulcer, 31 with gastroduodenal ulcer with gastritis, 27 with gastritis, 3 with gastric polyps and 8 with gastric cancer. Results were compared with 20 healthy control subjects who were endoscopically normal. Two specimens each were taken from 3 sites in the stomach. One part was used for a histological study to examine the presence of the organisms. The other part was cultured using Skirrow's agar microaerophilically. Conventional microflora and C. pylori were examined in gastric contents of some cases. Bacteriological features of isolated strains of C. pylori were identical to the NCTC strain. C. pylori was the most dominant organism in gastric contents at any pH level. Detection rates of C. pylori by bacteriological culture were 96% in gastric ulcer, 100% in duodenal ulcer, 80% in coexisting gastroduodenal ulcer, 84% in gastroduodenal ulcer with gastritis, 70% in gastritis, 100% in gastric polyps and 100% in gastric cancer, and the percentages recognized by histological studies were 81, 100, 100, 84, 71, 67, and 57%, respectively. The values in healthy controls were 55% by histological and bacteriological methods (P less than 0.001 compared with overall ulcer patients). These results supported the close association between C. pylori and gastroduodenal diseases.

Adult↗
PubMed1989

Membrane structure in isolated and intact myelins.

The biochemical composition of myelin and the topology of its constituent lipids and proteins are typically studied using membranes that have been isolated from whole, intact tissue using procedures involving hypotonic shock and sucrose density gradient centrifugation. To what extent, however, are the structure and intermembrane interactions of isolated myelin similar to those of intact myelin? We have previously reported that intact and isolated myelins do not always show identical myelin periods, indicating a difference in membrane-membrane interactions. The present study addresses the possibility that this is due to altered membrane structure. Because x-ray scattering from isolated myelin sometimes consists of overlapping Bragg reflections or is continuous, we developed nonlinear least squares procedures for analyzing the total intensity distribution after film scaling, background subtraction, and Lorentz correction. We calculated electron density profiles of isolated myelin for comparison with membrane profiles from intact myelin. The change in the width of the extracellular space and the relative invariance of the cytoplasmic space as a function of pH and ionic strength that we previously found for intact nerve was largely paralleled by isolated myelin. There were two exceptions: isolated CNS myelin was resistant to swelling under all conditions, and isolated PNS myelin in hypotonic saline showed indefinite swelling at the extracellular apposition. However, electron density profiles of isolated myelins, calculated to 30 A resolution, did not show any major change in structure compared with intact myelin that could account for the differences in interactions.

Animals↗
PubMed1989

Myelin membrane structure and composition correlated: a phylogenetic study.

We have correlated myelin membrane structure with biochemical composition in the CNS and PNS of a phylogenetic series of animals, including elasmobranchs, teleosts, amphibians, and mammals. X-ray diffraction patterns were recorded from freshly dissected, unfixed tissue and used to determine the thicknesses of the liquid bilayer and the widths of the spaces between membranes at their cytoplasmic and extracellular appositions. The lipid and protein compositions of myelinated tissue from selected animals were determined by TLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis/immunoblotting, respectively. We found that (1) there were considerable differences in lipid (particularly glycolipid) composition, but no apparent phylogenetic trends; (2) the lipid composition did not seem to affect either the bilayer thickness, which was relatively constant, or the membrane separation; (3) the CNS of elasmobranch and teleost and the PNS of all four classes contained polypeptides that were recognized by antibodies against myelin P0 glycoprotein; (4) antibodies against proteolipid protein (PLP) were recognized only by amphibian and mammalian CNS; (5) wide extracellular spaces (ranging from 36 to 48 A) always correlated with the presence of P0-immunoreactive protein; (6) the narrowest extracellular spaces (approximately 31 A) were observed only in PLP-containing myelin; (7) the cytoplasmic space in PLP-containing myelin (approximately 31 A) averaged approximately 5 A less than that in P0-containing myelin; (8) even narrower cytoplasmic spaces (approximately 24 A) were measured when both P0 and 11-13-kilodalton basic protein were detected; (9) proteins immunoreactive to antibodies against myelin P2 basic protein were present in elasmobranch and teleost CNS and/or PNS, and in mammalian PNS, but not in amphibian tissues; and (10) among mammalian PNS myelins, the major difference in structure was a variation in membrane separation at the cytoplasmic apposition. These findings demonstrate which features of myelin structure have remained constant and which have become specifically altered as myelin composition changed during evolutionary development.

Animals↗
PubMed1989

Genetic studies on the inability of beta-galactosidase to be translocated across the Escherichia coli cytoplasmic membrane.

When a signal sequence is attached to beta-galactosidase, the normally cytoplasmic protein is unable to fully traverse the cytoplasmic membrane. We used a genetic approach to study those features of beta-galactosidase responsible for the block in translocation. By using both in vivo and in vitro techniques, fragments of beta-galactosidase were interposed between a signal sequence and alkaline phosphatase. The alkaline phosphatase acts as a sensor for any blocking effects of beta-galactosidase on export. From these studies, we show that multiple regions of beta-galactosidase contribute to its failure to be translocated. These results are most easily interpreted if the folding of beta-galactosidase or of domains of it is responsible for the block in export. In addition, in certain constructs, positively charged amino acids directly following the signal sequence interfered with export.

Alkaline Phosphatase↗
PubMed1989

Orientation of proteolipid protein in myelin: comparison of models with X-ray diffraction measurements.

Three models have been proposed for the arrangement of proteolipid protein (PLP) in the myelin membrane. We have tested these models by determining to what extent each is consistent with the membrane-membrane interactions and electron density profile of central nervous system myelin obtained from X-ray diffraction. Equilibrium periods and membrane separations were calculated from the proposed organization of lipids and proteins in the membrane, and compared with values obtained experimentally as a function of pH and ionic strength. The orientation of the proteins was also used to calculate electron density levels in the cytoplasmic and extracellular spaces. We found that the Stoffel and Hudson models for PLP were more consistent than the Laursen model with the range of pH over which the intermembrane separation at the extracellular apposition is a minimum. The Hudson model also fits better the swollen periods observed at alkaline pH. The Hudson PLP model has many more residues in the extracellular side of the membrane than does either of the other models, resulting in higher electron density in the extracellular space compared to the cytoplasmic space. Such an asymmetric distribution of electron density is offset by the electron density of myelin basic protein which is localized in the cytoplasmic space. The resulting similar levels of electron density at the two appositions are like those in profiles calculated from the X-ray data.

Animals↗
PubMed1988

Vectors that facilitate the expression and purification of foreign peptides in Escherichia coli by fusion to maltose-binding protein.

Vectors were constructed that allow foreign peptides to be expressed in Escherichia coli as fusion proteins. The peptides are fused to the C terminus of maltose-binding protein (MBP), which allows them to be purified by the MBP's affinity to cross-linked amylose (starch). The fusion protein can be directed to the periplasm by including the leader sequence from the phoA gene on the vector.

ATP-Binding Cassette Transporters↗
PubMed1988

Membrane interactions in nerve myelin. I. Determination of surface charge from effects of pH and ionic strength on period.

We have used x-ray diffraction to study the interactions between myelin membranes in the sciatic nerve (PNS) and optic nerve (CNS) as a function of pH (2-10) and ionic strength (0-0.18). The period of myelin was found to change in a systematic manner with pH and ionic strength. PNS periods ranged from 165 to 250 A or more, while CNS periods ranged from 150 to 230 A. The native periods were observed only near physiological ionic strength at neutral or alkaline pH. The smallest periods were observed in the pH range 2.5-4 for PNS myelin and pH 2.5-5 for CNS myelin. The minimum period was also observed for PNS myelin after prolonged incubation in distilled water. At pH 4, within these acidic pH ranges, myelin period increased slightly with ionic strength; however, above these ranges, the period increased with pH and decreased with ionic strength. Electron density profiles calculated at different pH and ionic strength showed that the major structural alteration underlying the changes in period was in the width of the aqueous space at the extracellular apposition of membranes; the width of the cytoplasmic space was virtually constant. Assuming that the equilibrium myelin periods are determined by a balance of nonspecific forces/i.e., the electrostatic repulsion force and the van der Walls attractive force, as well as the short-range repulsion force (hydration force, or steric stabilization), then values in the period-dependency curve can be used to define the isoelectric pH and exclusion length of the membrane. The exclusion length, which is related to the minimum period at isoelectric pH, was used to calculate the electrostatic repulsion force given the other forces. The electrostatic repulsion was then used to calculate the surface potential, which in turn was used to calculate the surface charge density (at different pH and ionic strength). We found the negative surface charge increases with pH at constant ionic strength and with ionic strength at constant pH. We suggest that the former is due to deprotonation of the ionizable groups on the surface while the latter is due to ion binding. Interpretation of our data in terms of the chemical composition of myelin is given in the accompanying paper (Inouye and Kirschner, 1988). We also calculated the total potential energy functions for the different equilibrium periods and found that the energy minima became shallower and broader with increasing membrane separation. Finally, it was difficult to account directly for certain structural transitions from a balance of nonspecific forces. Such transitions included the abrupt appearance of the native period at alkaline pH and physiological ionic strength and the discontinuous compaction after prolonged treatment in distilled water. Possibly, in PNS myelin conformational modification of PO glycoprotein occurs under these conditions. The invariance of the cytoplasmic space suggests the presence of specific short-range interactions between surfaces at this apposition.

Animals↗
PubMed1988

Membrane interactions in nerve myelin: II. Determination of surface charge from biochemical data.

In our accompanying paper (Inouye and Kirschner, 1988) we calculated the surface charge density at the extracellular surfaces in peripheral and central nervous system (PNS; CNS) myelins from observations on the dependency of the width of the extracellular space on pH and ionic strength. Here, we have determined the surface charge density of the membrane surfaces in myelin from its chemical composition and the localization of some of its molecular components. We then analyzed the attractive and repulsive forces between the apposed surfaces and calculated equilibrium periods for comparison with the measured values. The biochemical model accounts for the observed isoelectric range of the myelin period and, with the surface charge reduced (possibly by divalent cation binding or a space charge approximation), the model also accounts for the dependency of period on pH above the isoelectric range. At the extracellular (and cytoplasmic) surfaces the contribution of lipid (with pI approximately 2) to the net surface charge is about the same in both PNS and CNS myelin, whereas the contribution of protein depends on which ones are exposed at the two surfaces. The protein conformation and localization modulate the surface charge of the lipid, resulting in positively-charged cytoplasmic surfaces (pI approximately 9) and negatively-charged extracellular surfaces (pI approximately 2-4). The net negative charge at the extracellular surface is due in CNS myelin to lipid, and in PNS myelin to both lipid and (PO) glycoprotein. The net positive charge at the cytoplasmic surface is due in CNS myelin mostly to basic protein, and in PNS myelin to PO glycoprotein and basic protein. The invariance of the cytoplasmic packing may be due to specific short-range interactions. Our models demonstrate how the particular myelin proteins and their localization and conformation can account for the differences in inter-membrane interactions in CNS and PNS myelins.

Amino Acids↗