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M L Garcia

Publications and source records attributed to M L Garcia.

At least 55 records · Page 3Linked to original sources
PubMed1997

Margatoxin binds to a homomultimer of K(V)1.3 channels in Jurkat cells. Comparison with K(V)1.3 expressed in CHO cells.

Voltage-gated potassium (K(V)) channels play key roles in setting the resting potential and in the activation cascade of human peripheral T lymphocytes. Margatoxin (MgTX), a 39-amino acid peptide from Centruroides margaritatus, is a potent inhibitor of lymphocyte K(V) channels. The binding of monoiodotyrosinyl margatoxin ([125I]MgTX) to plasma membranes prepared from either Jurkat cells, a human leukemic T cell line, or CHO cells stably transfected with the Shaker-type voltage-gated K+ channel, K(V)1.3, has been used to investigate the properties of lymphocyte K(V) channels. These data were compared with [125I]MgTX binding to heterotetrameric K(V) channels in rat brain synaptic plasma membranes [Knaus, H. G., et al. (1995) Biochemistry 34, 13627-13634]. The affinity for [125I]MgTX is 100-200 fM in either Jurkat or CHO/K(V)1.3 membranes, and the receptor density is 20-120 fmol/mg in Jurkat membranes or 1000 fmol/mg in CHO/K(V)1.3 membranes. In contrast to rat brain, [125I]MgTX binding to Jurkat and CHO/K(V)1.3 membranes exhibits an absolute requirement for K+, with no potentiation of binding by Na+. K(V)1.3 was the only K(V)1 series channel present in either CHO/K(V)1.3 or Jurkat plasma membranes as determined by immunoprecipitation of [125I]MgTX binding or by Western blot analyses using sequence-specific antibodies prepared against members of the K(V)1 family. The relative potencies of a series of peptidyl K(V) channel inhibitors was essentially the same for inhibition of [125I]MgTX binding to Jurkat, CHO, or rat brain membranes and for blocking 86Rb+ efflux from the CHO/K(V)1.3 cells, except that alpha-dendrotoxin was more potent at blocking binding to rat brain membranes than in the other assays. The characteristics of [125I]MgTX binding, the antibody profiles, and the effects of the peptidyl K(V) inhibitors all indicate that the [125I]MgTX receptor in Jurkat lymphocytes is comprised of a homomultimer of K(V)1.3, unlike the heteromultimeric arrangement of the receptor in rat brain.

Animals↗
PubMed1997

[125I]Iberiotoxin-D19Y/Y36F, the first selective, high specific activity radioligand for high-conductance calcium-activated potassium channels.

Iberiotoxin (IbTX), a selective peptidyl ligand for high-conductance Ca2(+)-activated K+ (maxi-K) channels cannot be radioiodinated in biologically active form due to the importance of Y36 in interacting with the channel pore. Therefore, an IbTX double mutant (IbTX-D19Y/Y36F) was engineered, expressed in Escherichia coli, purified to homogeneity, and radiolabeled to high specific activity with 125I. IbTX-D19Y/Y36F and [127I]IbTX-D19Y/Y36F block maxi-K channels expressed in Xenopus laevis oocytes with equal potency as wild-type IbTX (Kd approximately 1 nM). Under low ionic strength conditions, [125I]IbTX-D19Y/Y36F binds with high affinity to smooth muscle sarcolemmal maxi-K channels (Kd of 5 pM as determined by either equilibrium binding or kinetic binding analysis), and with a binding site density of 0.45 pmol/mg of protein. Competition studies with wild-type IbTX, IbTX-D19Y/Y36F or charybdotoxin (ChTX) result in complete inhibition of binding whereas toxins selective for voltage-gated K+ channels (margatoxin (MgTX) or alpha-dendrotoxin (alpha-DaTX) do not have any effect on IbTX binding. Indole diterpene alkaloids, which are selective inhibitors of maxi-K channels, and potassium ions both modulate [125I]IbTX-D19Y/Y36F binding in a complex manner. This pattern is also reflected during covalent incorporation of the radiolabeled toxin into the 31 kDa beta-subunit of the maxi-K channel in the presence of a bifunctional cross-linking reagent. In rat brain membranes, IbTX-D19Y/Y36F does not displace binding of [125I]MgTX or [125I]-alpha-DaTX to sites associated with voltage-gated K+ channels, nor do these latter toxins inhibit [125I]IbTX-D19Y/Y36F binding. Taken together, these results demonstrate that [125I]IbTX-D19Y/Y36F is the first selective radioligand for maxi-K channels with high specific activity.

Amino Acid Sequence↗
PubMed1997

Seizure-induced alterations of plasma membrane calcium ATPase isoforms 1, 2 and 3 mRNA and protein in rat hippocampus.

Improper intracellular regulation of the ubiquitous second messenger, calcium, has been linked to several pathological conditions. The plasma membrane calcium ATPase (PMCA) is one of the primary systems for translocating calcium from the cytosol to the extracellular milieu. As an initial assessment of the possible involvement of PMCAs in kainate (KA)-induced neurodegeneration, we have determined the effect of KA-induced seizures upon PMCA mRNA and protein. In situ hybridization was performed on tissue from adult male Sprague-Dawley rats sacrificed at various time points following i.p. injection of KA. KA altered the expression within the hippocampal subfields for mRNAs of PMCA isoforms 1 and 2. PMCA 1 and 2 mRNAs exhibited hybridization below control levels 12-48 h post-injection within CA1 and CA3. Within the dentate gyrus, PMCA 2 mRNA hybridized below control levels 4 h post-injection, but recovered to control levels by 24 h post-injection. Alterations in combined PMCA protein levels occurred at all time points examined post-injection. These observations provide evidence that KA-induced seizures alter the PMCAs at the mRNA and protein levels, suggesting a possible role for this calcium efflux system in the neuronal degeneration inherent to this paradigm.

Animals↗
PubMed1997

Acute orbital myositis. Case report.

The case of 22-year old, white woman with bilateral orbital myositis following an acute upper respiratory tract infection is reported. The most important clinical findings were ocular pain, proptosis, restricted eye motility and swelling of the eyelids. The enlarged eye muscles were seen on orbital computerized tomography scan. The clinical findings of inflammatory orbital myositis and clinical response to corticotherapy are emphasized.

Acute Disease↗
PubMed1996

Distribution of high-conductance Ca(2+)-activated K+ channels in rat brain: targeting to axons and nerve terminals.

Tissue expression and distribution of the high-conductance Ca(2+)-activated K+ channel Slo was investigated in rat brain by immunocytochemistry, in situ hybridization, and radioligand binding using the novel high-affinity (Kd 22 pM) ligand [3H]iberiotoxin-D19C ([3H]IbTX-D19C), which is an analog of the selective maxi-K peptidyl blocker IbTX. A sequence-directed antibody directed against Slo revealed the expression of a 125 kDa polypeptide in rat brain by Western blotting and precipitated the specifically bound [3H]IbTX-D19C in solubilized brain membranes. Slo immunoreactivity was highly concentrated in terminal areas of prominent fiber tracts: the substantia nigra pars reticulata, globus pallidus, olfactory system, interpeduncular nucleus, hippocampal formation including mossy fibers and perforant path terminals, medial forebrain bundle and pyramidal tract, as well as cerebellar Purkinje cells. In situ hybridization indicated high levels of Slo mRNA in the neocortex, olfactory system, habenula, striatum, granule and pyramidal cell layer of the hippocampus, and Purkinje cells. The distribution of Slo protein was confirmed in microdissected brain areas by Western blotting and radioligand-binding studies. The latter studies also established the pharmacological profile of neuronal Slo channels. The expression pattern of Slo is consistent with its targeting into a presynaptic compartment, which implies an important role in neural transmission.

Amino Acid Sequence↗
PubMed1996

High-conductance calcium-activated potassium channels; structure, pharmacology, and function.

High-conductance calcium-activated potassium (maxi-K) channels comprise a specialized family of K+ channels. They are unique in their dual requirement for depolarization and Ca2+ binding for transition to the open, or conducting, state. Ion conduction through maxi-K channels is blocked by a family of venom-derived peptides, such as charybdotoxin and iberiotoxin. These peptides have been used to study function and structure of maxi-K channels, to identify novel channel modulators, and to follow the purification of functional maxi-K channels from smooth muscle. The channel consists of two dissimilar subunits, alpha and beta. The alpha subunit is a member of the slo Ca(2+)-activated K+ channel gene family and forms the ion conduction pore. The beta subunit is a structurally unique, membrane-spanning protein that contributes to channel gating and pharmacology. Potent, selective maxi-K channel effectors (both agonists and blockers) of low molecular weight have been identified from natural product sources. These agents, together with peptidyl inhibitors and site-directed antibodies raised against alpha and beta subunit sequences, can be used to anatomically map maxi-K channel expression, and to study the physiologic role of maxi-K channels in various tissues. One goal of such investigations is to determine whether maxi-K channels represent novel therapeutic targets.

Amino Acid Sequence↗
PubMed1996

NodZ of Bradyrhizobium extends the nodulation host range of Rhizobium by adding a fucosyl residue to nodulation signals.

The nodulation genes of rhizobia are involved in the production of the lipo-chitin oligosaccharides (LCO), which are signal molecules required for nodule formation. A mutation in nodZ of Bradyrhizobium japonicum results in the synthesis of nodulation signals lacking the wild-type 2-O-methylfucose residue at the reducting-terminal N-acetylglucosamine. This phenotype is correlated with a defective nodulation of siratro (Macroptilium atropurpureum). Here we show that transfer of nodZ to Rhizobium leguminosarum blovar (bv) viciae, which produces LCOs that are not modified at the reducing-terminal N-acetylglucosamine, results in production of LCOs with a fucosyl residue on C-6 of the reducing-terminal N-acetylglucosamine. This finding, together with in vitro enzymatic assays, indicates that the product of nodZ functions as a fucosyltransferase. The transconjugant R. leguminosarum strain producing fucosylated LCOs acquires the capacity to nodulate M. atropurpureum, Glycine soja, Vigna unguiculate and Leucaena leucocephala. Therefore, nodZ extends the narrow host range of R. leguminosarum bv. viciae to include various tropical legumes. However, microscopic analysis of nodules induced on siratro shows that these nodules do not contain bacteroids, showing that transfer of nodZ does not allow R. leguminosarum to engage in a nitrogen-fixing symbiosis with this plant.

Amino Acid Sequence↗
PubMed1996

Accumulation of alfalfa mosaic virus RNAs 1 and 2 requires the encoded proteins in cis.

RNAs 1 and 2 of the tripartite genome of alfalfa mosaic virus (A1MV) encode the replicase proteins P1 and P2, respectively. P1 expressed in transgenic plants (P1 plants) can be used in trans to support replication of A1MV RNAs 2 and 3, and P2 expressed in transgenic plants (P2 plants) can be used in trans to support replication of A1MV RNAs 1 and 3. Wild-type RNA 1 was able to coreplicate with RNAs 2 and 3 in P1 plants, but this ability was abolished by frameshifts or deletions in the P1 gene of RNA 1. Similarly, wild-type RNA 2 coreplicated with RNAs 1 and 3 in P2 plants, but frameshifts or deletions in the P2 gene of RNA 2 interfered with this replication. Apparently, the P1 and P2 genes are required in cis for the accumulation of RNAs 1 and 2, respectively. Point mutations in the GDD motif of the P2 gene in RNA 2 interfered with accumulation of RNA 2 in P2 plants, indicating that replication of RNA 2 is linked to its translation into a functional protein. Plants transformed with both the P1 and P2 genes (P12 plants) accumulate replicase activity that is able to replicate RNA 3 in trans. An analysis of the time course of the accumulation of RNAs 1, 2, and 3 in protoplasts of P12 plants supported the conclusion that translation and replication are tightly coupled for A1MV RNAs 1 and 2 but not for RNA 3.

Alfalfa mosaic virus↗
PubMed1995

Functional reconstitution of the large-conductance, calcium-activated potassium channel purified from bovine aortic smooth muscle.

The charybdotoxin (ChTX) receptor has been purified from bovine aortic smooth muscle using conventional chromatographic techniques and sucrose gradient centrifugation. Fractions from the final sucrose gradient purification were enriched in specific binding of monoiodinated ChTX (125i-ChTX) approximately 2000-fold over native sarcolemmal membranes. The ChTX binding activity correlated with the presence of two polypeptides of 65 (alpha) and 31 (beta) kDa. Using the cross-linking reagent, disuccinimidyl suberate, 125I-ChTX was specifically incorporated into a polypeptide of approximately 31 kDa. Cross-linking and binding of 125I-ChTX to the purified ChTX receptor was inhibited by ChTX, iberiotoxin (IbTX), and tetraethylammonium (TEA). Liposomes containing the purified ChTX receptor were incorporated into planar lipid bilayers. In symmetric 150 mM KC1, the channels observed were > 20-fold more selective for potassium over sodium and exhibited a large, single-channel conductance of 323 +/- 2.5 pS in charged lipids and 249 +/- 7 pS in neutral lipids. Depolarizing membrane potentials increased the open probability of the purified channels e-fold per 11.5 +/- 0.3 mV, while intracellular calcium increased the open probability according to a third power (2.9 +/- 0.2) relationship. Mean channel closed durations decreased while open times slightly increased as membrane potential and calcium concentration were elevated. The distributions of open and closed durations were well described by the sums of three and five to six exponential components, respectively. Purified maxi-K channels were blocked with micromolar affinity by external TEA and with nanomolar affinity by extracellular IbTX and ChTX. Kinetics of ChTX block of the purified channel revealed an equilibrium dissociation constant for toxin block 4.6 +/- 0.7 nM under conditions of physiological ionic strength. The purified maxi-K channel displays many of the biophysical and pharmacological properties of maxi-K channels derived from native tissue.

Animals↗
PubMed1995

[125I]margatoxin, an extraordinarily high affinity ligand for voltage-gated potassium channels in mammalian brain.

Monoiodotyrosine margatoxin ([125I]MgTX) specifically and reversibly labels a maximum of 0.8 pmol of sites/mg of protein in purified rat brain synaptic plasma membrane vesicles with a dissociation constant of 0.1 pM under equilibrium binding conditions. This Kd value was confirmed by kinetic experiments (Kd of 0.07 pM), competition assays employing native margatoxin (MgTX) (Ki of 0.15 pM), and receptor saturation studies (Kd of 0.18 pM). Thus, this toxin represents the highest affinity, reversible radioligand for any membrane-bound receptor or ion channel described to date. [125I]MgTX binding in this system is modulated by charybdotoxin (Ki of 5 pM), kaliotoxin (Ki of 1.5 pM), and the agitoxins I and II (Ki's of 0.1 and 0.3 pM, respectively), in a noncompetitive manner. Moreover, alpha-dendrotoxin displayed a Ki value of 0.5 pM. Iberiotoxin was without any effect, suggesting that the receptor site is likely to be associated with a voltage-gated K+ channel complex. [125I]MgTX binding is inhibited by cations that are established blockers of voltage-dependent K+ channels (Ba2+, Ca2+, Cs+). The monovalent cations Na+ and K+ stimulate binding at low concentrations before producing complete inhibition as their concentrations are increased. Stimulation of binding results from an allosteric interaction that decreases Kd, whereas inhibition is due to an ionic strength effect. Affinity labeling of the binding site in rat brain synaptic plasma membranes employing [125I]MgTX and the bifunctional cross-linking reagent, disuccinimidyl suberate, causes specific and covalent incorporation of toxin into a glycoprotein of an apparent molecular weight (M(r)) of 74,000. Deglycosylation studies reveal an M(r) for the core polypeptide of the MgTX receptor of 63,000.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Characterization of tissue-expressed alpha subunits of the high conductance Ca(2+)-activated K+ channel.

Purified high conductance calcium-activated potassium (maxi-K) channels from tracheal smooth muscle have been shown to consist of a 60-70-kDa alpha subunit, encoded by the slo gene, and a 31-kDa beta subunit. Although the size of the beta subunit is that expected for the product of the gene encoding this protein, the size of the alpha subunit is smaller than that predicted from the slo coding region. To determine the basis for this discrepancy, sequence-directed antibodies have been raised against slo. These antibodies specifically precipitate the in vitro translation product of mslo, which yields an alpha subunit of the expected molecular mass (135 kDa). Immunostaining experiments employing smooth muscle sarcolemma, skeletal muscle T-tubules, as well as membranes derived from GH3 cells reveal the presence of an alpha subunit with an apparent molecular mass of 125 kDa. The difference in size of the alpha subunit as expressed in these membranes and the purified preparations is due to a highly reproducible proteolytic decay that occurs mostly at an advanced stage of the maxi-K channel purification. In the purified maxi-K channel preparations investigated, the full-length alpha subunit, an intermediate size product of 90 kDa, and the 65-kDa polypeptide, as well as other smaller fragments can be detected using appropriate antibodies. Proteolysis occurs exclusively at two distinct positions within the long C-terminal tail of slo. In addition, evidence for the tissue expression of distinct splice variants in membrane-bound as well as purified maxi-K channels is presented.

Amino Acid Sequence↗
PubMed1995

Cross-linking of charybdotoxin to high-conductance calcium-activated potassium channels: identification of the covalently modified toxin residue.

High-conductance calcium-activated potassium (maxi-K) channels are composed of two subunits, alpha and beta. The pore-forming alpha subunit is a member of the mSlo family of K+ channels, whereas the beta subunit is a novel protein that modulates the biophysical and pharmacological properties of the channel complex. In the presence of a bifunctional cross-linking reagent, monoiodotyrosine charybdotoxin ([125I]ChTX) is covalently incorporated specifically into Lys69 of the beta subunit, which is located in a large extracellular loop of this protein. Using variants of ChTX which retain their channel-blocking activity and in which individual Lys residues have been mutated, we have identified the corresponding amino acid in ChTX that is involved in the cross-linking reaction. All of the ChTX mutants investigated bind to the maxi-K channel and display the same pharmacological profile as native ChTX in competition binding experiments. Whereas substitution of amino acids at positions 11 and 31 of ChTX yields wild-type cross-linking patterns, the peptide without a Lys at position 32 fails to incorporate into the beta subunit of the maxi-K channel. Given the model for the interaction between ChTX and the outer vestibule of the maxi-K channel that has been proposed (Stampe et al., 1994), our data constrain the maximum distance between the pore of this channel and the region in the extracellular loop of the beta subunit where the cross-linking reaction takes place to 11 A. This topological limit helps define structural features of the maxi-K channel that may aide in probing the functional interaction between alpha and beta subunits of the channel complex.

Animals↗
PubMed1995

L-735,334, a novel sesquiterpenoid potassium channel-agonist from Trichoderma virens.

A novel oleic acid ester of the carotane sesquiterpene 14-hydroxy CAF-603 was isolated from Trichoderma virens grown in a solid brown rice-based medium, a solid millet-based medium, or a mannitol-based liquid medium. Its structure was determined on the basis of ms and nmr analysis. It retains distinct biological activity on the high conductance calcium-activated potassium channel, unlike its analogues 14-hydroxy CAF-603, CAF-603 3-oleate, or CAF-603 3-linoleate.

Animals↗
PubMed1995

Neuroretinitis, aseptic meningitis, and lymphadenitis associated with Bartonella (Rochalimaea) henselae infection in immunocompetent patients and patients infected with human immunodeficiency virus type 1.

Bartonella (Rochalimaea) henselae causes a variety of diseases, including bacillary angiomatosis, peliosis hepatis, lymphadenitis, aseptic meningitis with bacteremia, and cat-scratch disease (CSD). Cases of B. henselae-related disease were collected from September 1991 through November 1993. Patients with suspected CSD, unexplained fever and lymphadenitis, or suspected B. henselae infection who were seen in the Infectious Diseases Clinic at Wilford Hall Medical Center (Lackland Air Force Base, TX) underwent physical and laboratory examinations. In addition to three previously described cases, 23 patients with R. henselae-related infection were identified. The patients included 19 immunocompetent individuals presenting with lymphadenitis (11), stellate neuroretinitis (5), Parinaud's oculoglandular syndrome with retinitis (1), chronic fatigue syndrome-like disease (1), and microbiologically proven adenitis without the presence of immunofluorescent antibodies to B. henselae (1) and four patients infected with human immunodeficiency virus type 1 presenting with isolated lymphadenitis (1), diffuse upper-extremity adenitis (1), neuroretinitis (1), and aseptic meningitis (1). A couple with neuroretinitis and their pet cat, a persistently fatigued patient, and a patient with Parinaud's oculoglandular syndrome were shown to have bacteremia. Tissue cultures were positive for B. henselae in three recent cases of adenitis. Twenty-two patients were exposed to cats. This series further demonstrates the similarities between B. henselae-related diseases and CSD and identifies several new syndromes due to B. henselae.

Adolescent↗
PubMed1995

Charybdotoxin and its effects on potassium channels.

Over the last few years, a considerable amount of information has been obtained regarding K+ channels. Different areas of research have contributed to knowledge in this field. Charybdotoxin (ChTX), a 37-amino acid peptide isolated from venom of the scorpion Leiurus quinquestriatus var. hebraeus, represents a remarkable tool for studying K+ channels. With its use, it has been possible to purify the high-conductance Ca(2+)-activated K+ (maxi-K) channel to homogeneity and determine the subunit composition of this channel. This has led to the discovery of an auxiliary beta-subunit that, when coexpressed with the pore-forming subunit, mSlo, alters the biophysical and pharmacological properties of this latter subunit. With the feasibility of producing large amounts of ChTX by recombinant techniques and the knowledge of the three-dimensional structure of the peptide, it has been possible to carry out site-directed mutagenesis studies and obtain a picture of the interaction surface of the toxin with two channels, maxi-K and Shaker, and to derive a picture of the complementary surface of the receptor in these two channels. Finally, ChTX, and the more selective K+ channel toxins that were subsequently discovered, have provided us with unique tools not only to determine the functional role that K+ channels play in target tissues but also to develop the molecular pharmacology of these channels.

Amino Acid Sequence↗
PubMed1995

Characterization of and modulation by a beta-subunit of a human maxi KCa channel cloned from myometrium.

cDNAs encoding functional maxi KCa channel alpha-subunits (hslo) were cloned from human myometrium. Northern blot analysis revealed a high abundance of mRNA in human uterine smooth muscle. Calcium- and voltage-activated K+ currents were recorded from Xenopus laevis oocytes injected with hslo cRNA and compared with currents after reconstitution of oocyte membranes expressing cloned maxi KCa channels. The expressed channels displayed characteristics of native maxi KCa channels, including large conductance (280 pS in symmetrical 110 mM K+), calcium sensitivity, kinetics and pharmacology. Currents were activated by niflumic acid; blocked by tetraethylammonium, charybdotoxin and iberiotoxin; and were insensitive to lemakalim, pinacidil, apamin and 4-aminopyridine. Coexpression with the beta-subunit, cloned from bovine trachea smooth muscle, dramatically increased the apparent calcium sensitivity as evident from a leftward shift of the voltage-activation curves. Half maximal activation (V1/2), measured in 10 microM Ca2+, was 12 +/- 18 mV (+/- SD, n = 62) for the alpha-subunit alone and -87 +/- 10 mV (+/- SD, n = 39) in presence of the beta-subunit.

Animals↗
PubMed1994

Covalent attachment of charybdotoxin to the beta-subunit of the high conductance Ca(2+)-activated K+ channel. Identification of the site of incorporation and implications for channel topology.

Purified high conductance Ca(2+)-activated K+ (maxi-K) channels from bovine tracheal smooth muscle have been covalently labeled employing monoiodotyrosine charybdotoxin ([125I]ChTX) and different bifunctional cross-linking reagents. [125I]ChTX was specifically incorporated into the beta-subunit, which was thereafter isolated by size exclusion high performance liquid chromatography. Proteolytic fragments of the [125I]ChTX-labeled beta-subunit were generated by digestion with various endoproteinases. Glu-C or Asp-N cleavage yielded a glycosylated [125I]ChTX-labeled fragment of 13-14 kDa. A site-directed antiserum raised against residues 62-75 of the cloned beta-subunit of the maxi-K channel specifically recognizes the beta-subunit in immunostaining experiments and was capable of immunoprecipitating these ChTX-labeled peptides. Lys-C cleavage resulted in two fragments of 16 and 28 kDa, respectively, which were both precipitated by anti-beta (62-75). However, only the 28-kDa fragment was recognized by anti-beta(118-132) and shown to carry double the amount of N-linked carbohydrates. Taken together, these data restrict the site of covalent incorporation of ChTX into the beta-subunit exclusively at Lys69, confirm the predicted topology of this subunit, and indicate that both canonical N-linked glycosylation sites are occupied with complex carbohydrates of 5-6 kDa each. We propose that an extracellularly located portion of the beta-subunit is located within 7.7 A of the ChTX receptor site and could even participate in the formation of this receptor by close apposition of its extracellular domain with structural elements provided by the alpha-subunit.

Amino Acid Sequence↗