Biomedical subjects

David H Russell

Publications and source records attributed to David H Russell.

At least 19 recordsLinked to original sources

PubMed2007

Biochemical and functional analyses of the human Toll-like receptor 3 ectodomain.

The structure of the human Toll-like receptor 3 (TLR3) ectodomain (ECD) was recently solved by x-ray crystallography, leading to a number of models concerning TLR3 function (Choe, J., Kelker, M. S., and Wilson, I. A. (2005) Science 309, 581-585; Bell, J. K., Botos, I., Hall, P. R., Askins, J., Shiloach, J., Segal, D. M., and Davies, D. R. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 10976-10980) The structure revealed four pairs of cysteines that are putatively involved in disulfide bond formation, several residues that are predicted to be involved in dimerization between ECD subunits, and surfaces that could bind to poly(I:C). In addition, there are two loops that protrude from the central solenoid structure of the protein. We examined the recombinant TLR3 ECD for disulfide bond formation, poly(I:C) binding, and protein-protein interaction. We also made over 80 mutations in the residues that could affect these features in the full-length TLR3 and examined their effects in TLR3-mediated NF-kappaB activation. A number of mutations that affected TLR3 activity also affected the ability to act as dominant negative inhibitors of wild type TLR3. Loss of putative RNA binding did not necessarily affect dominant negative activity. All of the results support a model where a dimer of TLR3 is the form that binds RNA and activates signal transduction.

Amino Acid Sequence↗

PubMed2006

Identification of the first neuropeptides from the CNS of Hemiptera: CAPA peptides of the southern green stinkbug Nezara viridula (L.).

A direct mass spectrometric investigation of nerve homologs of the abdominal perisympathetic organs was employed to reveal the first and complete sequences of CAPA peptides from a hemipteran species, the southern green stinkbug Nezara viridula. Side-chain fragmentations allowed the assignment of internal Leu/Ile; on-plate acetylation was used to distinguish between the mass-related Lys and Gln. The following sequences were obtained: DQLFPFPRV-NH(2) (CAPA-PVK-1), EQLIPFPRV-NH(2) (CAPA-PVK-2), and NGSAGNGGLWFGPRL/I-NH(2) (CAPA-PK). CAPA-PVKs are associated with the regulation of diuresis in insects, and identification of those native to a hemipteran will provide the experimental basis to better understand regulation of water balance in this family of insects.

Amino Acid Sequence↗

PubMed2006

Comparative studies of 193-nm photodissociation and TOF-TOFMS analysis of bradykinin analogues: the effects of charge site(s) and fragmentation timescales.

The dissociation reactions of [M + H]+, [M + Na]+, and [M + Cu]+ ions of bradykinin (amino acid sequence RPPGFSPFR) and three bradykinin analogues (RPPGF, RPPGFSPF, PPGFSPFR) are examined by using 193-nm photodissociation and post-source decay (PSD) TOF-TOF-MS techniques. The photodissociation apparatus is equipped with a biased activation cell, which allows us to detect fragment ions that are formed by dissociation of short-lived (<1 mus) photo-excited ions. In our previously reported photodissociation studies, the fragment ions were formed from ions dissociating with lifetimes that exceeded 10 mus; thus these earlier photofragment ion spectra and post-source decay (PSD) spectra [composite of both metastable ion (MI) and collision-induced dissociation (CID)] were quite similar. On the other hand, short-lived photo-excited ions dissociate by simple bond cleavage reactions and other high-energy dissociation channels. We also show that product ion types and abundances vary with the location of the charge on the peptide ion. For example, H+ and Na+ cations can bind to multiple polar functional groups (basic amino acid side chains) of the peptide, whereas Cu+ ions preferentially bind to the guanidino group of the arginine side-chain and the N-terminal amine group. Furthermore, when Cu+ is the charge carrier, the abundances of non-sequence informative ions, especially loss of small neutral molecules (H2O and NH3) is decreased for both photofragment ion and PSD spectra relative to that observed for [M + H]+ and [M + Na]+ peptide ions.

Amino Acid Sequence↗

PubMed2005

Identification of PVK/CAP2b neuropeptides from single neurohemal organs of the stable fly and horn fly via MALDI-TOF/TOF tandem mass spectrometry.

MALDI-TOF/TOF tandem mass spectrometry has been applied to determine the complete sequences of the PVK/CAP2b neuropeptides in the stable fly Stomoxys calcitrans and horn fly Haematobia irritans, insect pests of livestock. This peptidomic analysis of single neurohemal organ preparations allows the unambiguous assignment of internal Leu/Ile positions not distinguishable by previous mass spectrometric techniques. The sequences are as follows: Stoca-PVK/CAP2b-1, AGGASGLYAFPRVa; Stoca-PVK/CAP2b-2, NAKLYPVPRVa; and Haeir-PVK/CAP2b-1, AGGASGLYAFPRVa; Haeir-PVK/CAP2b-1, NAKLYPMPRVa. Both Stoca-PVK/CAP2b-1 and -2 stimulate Malpighian tubule fluid secretion in the stable fly, with EC50 values between 3 and 11 nM. The identification of these novel neuropeptides adds to our knowledge of the peptidomes of flies, and can aid in the development of neuropeptide-based control strategies of these insect pests.

Amino Acid Sequence↗

PubMed2005

Anion template effect on the self-assembly and interconversion of metallacyclophanes.

Reactions of 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine (bptz) with solvated first-row transition metals M(II) (M(II) = Ni, Zn, Mn, Fe, Cu) have been explored with emphasis on the factors that influence the identity of the resulting cyclic products for Ni(II) and Zn(II). The relatively small anions, namely [ClO4]- and [BF4]-, lead to the formation of molecular squares [{M4(bptz)4(CH3CN)8} subsetX][X]7, (M = Zn(II), Ni(II); X = [BF4]-, [ClO4]-), whereas the larger anion [SbF6]- favors the molecular pentagon [{Ni5(bptz)5-(CH3CN)10} subsetSbF6][SbF6]9. The molecular pentagon easily converts to the square in the presence of excess [BF4]-, [ClO4]-, and [I]- anions, whereas the Ni(II) square can be partially converted to the less stable pentagon under more forcing conditions in the presence of excess [SbF6]- ions. No evidence for the molecular square being in equilibrium with the pentagon was observed in the ESI-MS spectra of the individual square and pentagon samples. Anion-exchange reactions of the encapsulated ion in [{Ni4(bptz)4(CH3CN)8} subsetClO4][ClO4]7 reveal that a larger anion such as [IO4]- cannot replace [ClO4]- inside the cavity, but that the linear [Br3]- anion is capable of doing so. ESI-MS studies of the reaction between [Ni(CH3CN)6][NO3]2 and bptz indicate that the product is trinuclear. Mass spectral studies of the bptz reactions with Mn(II), Fe(II), and Cu(II), in the presence of [ClO4]- anions, support the presence of molecular squares. The formation of the various metallacyclophanes is discussed in light of the factors that influence these self-assembly reactions, such as choice of metal ion, anion, and solvent.

Anions↗

PubMed2005

Functional analysis of RNA binding by the hepatitis C virus RNA-dependent RNA polymerase.

Protein-RNA interaction plays a critical role in regulating RNA synthesis by the hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp). RNAs of 7 nucleotides (nt) or longer had affinities 5-fold better than an RNA of 5 nt, suggesting a minimal length required for binding. To identify RNA contact sites on the HCV RdRp, a biotinylated 7-nt RNA capable of directing de novo initiation was used in a process that coupled reversible formaldehyde cross-linking, RNA affinity chromatography, and mass spectrometry. By this process, we identified 18 peptides cross-linked to the 7-nt RNA. When these identified peptides were overlaid on the three-dimensional structures of NS5B, most mapped to the fingers subdomain, connecting loops between fingers and thumb subdomains and in the putative RNA binding channel. Two of the identified peptides resided in the active site cavity of the RdRp. Recombinant HCV RdRp with single residue changes in likely RNA contact sites were generated and characterized for effects on HCV RdRp activity. Mutant proteins had significant effects on cross-linking to 7-nt RNA and reduced RNA synthesis in vitro by 2- to 20-fold compared with wild type protein. When the mutations were tested for the replication of HCV RNA in the context of the cells transfected with the HCV subgenomic replicon, all except one prevented colony formation, indicating a defect in HCV RNA replication. These biochemical and functional analyses identified a number of residues in the HCV RdRp that are important for HCV RNA synthesis.

Amino Acid Substitution↗

PubMed2005

Isolation and characterization of two disintegrins inhibiting ADP-induced human platelet aggregation from the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake).

Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are nonenzymatic proteins that inhibit cell-cell interactions, cell-matrix interactions, and signal transduction, and may have potential in the treatment of strokes, heart attacks, cancers, and osteoporosis. Prior to 1983, the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake) was known to be only neurotoxic; however, now there is evidence that these snakes can contain venom with: (1) neurotoxins; (2) hemorrhagins; and (3) both neurotoxins and hemorrhagins. In this study, two disintegrins, mojastin 1 and mojastin 2, from the venom of a Mohave rattlesnake collected in central Arizona (Pinal County), were isolated and characterized. The disintegrins in these venoms were identified by mass-analyzed laser desorption ionization/time-of-flight/time-of-flight (MALDI/TOF/TOF) mass spectrometry as having masses of 7.436 and 7.636 kDa. Their amino acid sequences are similar to crotratroxin, a disintegrin isolated from the venom of the western diamondback rattlesnake (C. atrox). The amino acid sequence of mojastin 1 was identical to the amino acid sequence of a disintegrin isolated from the venom of the Timber rattlesnake (C. horridus). The disintegrins from the Mohave rattlesnake venom were able to inhibit ADP-induced platelet aggregation in whole human blood both having IC50s of 13.8 nM, but were not effective in inhibiting the binding of human urinary bladder carcinoma cells (T24) to fibronectin.

Adenosine Diphosphate↗

PubMed2005

Mass spectrometric assignment of Leu/Ile in neuropeptides from single neurohemal organ preparations of insects.

Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF-TOF) tandem mass spectrometry has been applied for the first time on an insect/arthropod target, focusing on PVK/CAP2b neuropeptides in the housefly Musca domestica and flesh fly Neobellieria bullata. The peptidomic analysis of single neurohemal organ preparations allows the unambiguous assignment of internal Leu/Ile positions not distinguishable by previous mass spectrometric techniques. The confirmation of side-chain fragments which allows assignment of Leu/Ile even from samples as small as neurohemal organs will greatly accelerate the identification of novel neuropeptides that are implicated in the regulation of critical physiological processes in insects. The unnatural Ile analog is 4.5 times more active than the native Leu sequence in a housefly Malpighian tubule fluid secretion assay, which reinforces the caveat that potency values in a biological assay cannot be relied upon to predict the native sequence.

Animals↗

PubMed2005

Size-selected (2-10 nm) gold nanoparticles for matrix assisted laser desorption ionization of peptides.

In this report, first use of size-selected gold nanoparticles (AuNPs) as matrixes for matrix assisted laser desorption/ionization (MALDI) is described for peptides and proteins. In comparison with conventional organic acid MALDI matrixes, the optimum matrix-to-analyte ratio with AuNP matrixes is reduced by 10-14 orders of magnitude. Significant differences in the relative abundances of the ions observed in positive and negative mode MALDI-time-of-flight mass spectrometry (TOFMS) are revealed as the AuNP size distribution is decreased from 10 to 2 nm, whereby 2-nm AuNPs exhibit quantum confinement effects prevalent in quantum dots. AuNP matrixes allow for selective analyte ionization, as demonstrated in the selective MALDI-TOFMS of phosphotyrosine in a background of phosphoserine and phosphothreonine peptides.

Gold↗

PubMed2005

Disintegrin, hemorrhagic, and proteolytic activities of Mohave rattlesnake, Crotalus scutulatus scutulatus venoms lacking Mojave toxin.

Venom from the Mohave rattlesnake, Crotalus scutulatus scutulatus, has been reported to be either: (1) neurotoxic; (2) hemorrhagic, or both (3) neurotoxic and hemorrhagic. In this study, 14 Mohave rattlesnakes from Arizona and Texas (USA) were analyzed for the presence of disintegrins and Mojave toxin. All venom samples were analyzed for the presence of hemorrhagic, proteolytic and disintegrin activities. The venoms were each chromatographed by reverse phase and their fractions tested for disintegrin activity. All specimens containing Mojave toxin were the most toxic and lacked proteolytic, hemorrhagic and disintegrin activities. In contrast, the venoms containing these activities lacked Mojave toxin. Two disintegrin genes, scutustatin and mojavestatin, were identified by PCR of genomic sequences. Scutustatin is a highly conserved disintegrin, while mojavestatin shows low conservation to other known disintegrins. Venoms with the highest LD50 measurements lacked both disintegrin genes, while the specimens with intermediate and low LD50 contained both genes. The intermediate LD50 group contained Mojave toxin and both disintegrin genes, but lacked hemorrhagic and disintegrin activity. Our results raise the possibility that scutustatin and mojavestatin are not expressed in the intermediate LD50 group, or that they may not be the same disintegrins responsible for the disintegrin activity found in the venom. Therefore, it is possible that Mohave rattlesnakes may produce more than two disintegrins.

Amino Acid Sequence↗

PubMed2005

The influence and utility of varying field strength for the separation of tryptic peptides by ion mobility-mass spectrometry.

The influence of field strength on the separation of tryptic peptides by drift tube-based ion mobility-mass spectrometry is reported. Operating the ion mobility drift tube at elevated field strengths (expressed in V cm(-1) torr(-1)) reduces separation times and increases ion transmission efficiencies. Several accounts in the literature suggest that performing ion mobility separation at elevated field strength can change the selectivity of ion separation. To evaluate the field strength dependant selectivity of ion mobility separation, we examined a data set of 65 singly charged tryptic peptide ion signals (mass range 500-2500 m/z) at six different field strengths and four different drift gas compositions (He, N2, Ar, and CH4). Our results clearly illustrate that changing the field strength from low field (15 V cm(-1) torr(-1)) to high field (66 V cm(-1) torr(-1)) does not significantly alter the selectivity or peak capacity of IM-MS. The implications of these results are discussed in the context of separation methodologies that rely on the field strength dependence of ion mobility for separation selectivity, e.g., high-field asymmetric ion mobility spectrometry (FAIMS).

Amino Acid Sequence↗

PubMed2005

The structure of gas-phase bradykinin fragment 1-5 (RPPGF) ions: an ion mobility spectrometry and H/D exchange ion-molecule reaction chemistry study.

Ion mobility-mass spectrometry (IM-MS) data is interpreted as evidence that gas-phase bradykinin fragment 1-5 (BK1-5, RPPGF) [M + H](+) ions exist as three distinct structural forms, and the relative abundances of the structural forms depend on the solvent used to prepare the matrix-assisted laser desorption ionization (MALDI) samples. Samples prepared from organic rich solvents (90% methanol/10% water) yield ions having an ion mobility arrival-time distribution (ATD) that is dominated by a single peak; conversely, samples prepared using mostly aqueous solvents (10% methanol/90% water) yield an ATD composed of three distinct peaks. The BK1-5 [M + H](+) ions were also studied by gas-phase hydrogen/deuterium (H/D) exchange ion-molecule reactions and this data supports our interpretation of the IM-MS data. Plausible structures for BK1-5 ions were generated by molecular dynamics (MD). Candidate MD-generated structures correlated to measured cross-sections suggest a compact conformer containing a beta-turn whereas a more extended, open form does not contain such an interaction. This study illustrates the importance of intra-molecular interactions in the stabilization of the gas-phase ions, and these results clearly illustrate that solution-phase parameters (i.e., MALDI sample preparation) greatly influence the structures of gas-phase ions.

Bradykinin↗

PubMed2005

Peptide sequencing by MALDI 193-nm photodissociation TOF MS.

Ultraviolet photodissociation time-of-flight (TOF) mass spectrometry (MS) is described as a method for determination of peptide ion primary structure. Monoisotopic selection and bond-specific activation, combined with the rapidity of TOF MS analysis, render this technique invaluable to the rapidly expanding field of proteomics. Photofragment ion spectra of model peptides acquired using both post-source decay (PSD) focusing and TOF-TOF experimental methods are exhibited. Advantages of 193-nm photodissociation for de novo sequencing of peptide ions are discussed.

Peptides↗

PubMed2004

A universal strategy for proteomic studies of SUMO and other ubiquitin-like modifiers.

Post-translational modification by the conjugation of small ubiquitin-like modifiers is an essential mechanism to affect protein function. Currently, only a limited number of substrates are known for most of these modifiers, thus limiting our knowledge of their role and relevance for cellular physiology. Here, we report the development of a universal strategy for proteomic studies of ubiquitin-like modifiers. This strategy involves the development of stable transfected cell lines expressing a double-tagged modifier under the control of a tightly negatively regulated promoter, the induction of the expression and conjugation of the tagged modifier to cellular proteins, the tandem affinity purification of the pool of proteins covalently modified by the tagged modifier, and the identification of the modified proteins by LC and MS. By applying this methodology to the proteomic analysis of SUMO-1 and SUMO-3, we determined that SUMO-1 and SUMO-3 are stable proteins exhibiting half-lives of over 20 h, demonstrated that sumoylation with both SUMO-1 and SUMO-3 is greatly stimulated by MG-132 and heat shock treatment, demonstrated the preferential usage of either SUMO-1 or SUMO-3 for some known SUMO substrates, and identified 122 putative SUMO substrates of which only 27 appeared to be modified by both SUMO-1 and SUMO-3. This limited overlapping in the subset of proteins modified by SUMO-1 and SUMO-3 supports that the SUMO paralogues are likely to be functionally distinct. Three of the novel putative SUMO substrates identified, namely the polypyrimidine tract-binding protein-associated splicing factor PSF, the structural microtubular component alpha-tubulin, and the GTP-binding nuclear protein Ran, were confirmed as authentic SUMO substrates. The application of this universal strategy to the identification of the pool of cellular substrates modified by other ubiquitin-like modifiers will dramatically increase our knowledge of the biological role of the different ubiquitin-like conjugations systems in the cell.

Amino Acid Sequence↗

PubMed2004

Analysis of phosphorylated peptides by ion mobility-mass spectrometry.

An ion mobility-mass spectrometry technique for rapid screening of phosphopeptides in protein digests is described. A data set of 43 sequences (ranging in mass from 400 to 3000 m/z) of model and tryptic peptides, including serine, threonine, and tyrosine phosphorylation, was investigated, and the data support our previously reported observation (Ruotolo, B. T.; Verbeck, G. F., IV; Thomson, L. M.; Woods, A. S.; Gillig, K. J.; Russell, D. H. J. Proteome Res. 2002, 1, 303.) that the drift time-m/z relationship for singly charged phosphorylated peptide ions is different from that for nonphosphorylated peptides. The data further illustrate that a combined data-dependent IM-MS/MS approach for phosphopeptide screening would have enhanced throughput over conventional MS/MS-based methodologies.

Amino Acid Sequence↗

PubMed2004

Binding of DNA purine sites to dirhodium compounds probed by mass spectrometry.

The adducts formed between the antitumor active compounds [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2), Rh(2)(O(2)CCH(3))(4), and Rh(2)(O(2)CCF(3))(4) with DNA oligonucleotides have been assessed by matrix-assisted laser desorption ionization (MALDI) and nanoelectrospray (nanoESI) coupled to time-of-flight mass spectrometry (TOF MS). A series of MALDI studies performed on dipurine (AA, AG, GA, and GG)-containing single-stranded oligonucleotides of different lengths (tetra- to dodecamers) led to the establishment of the relative reactivity cis-[Pt(NH(3))(2)(OH(2))(2)](2+) (activated cisplatin) approximately Rh(2)(O(2)CCF(3))(4) > cis-[Pt(NH(3))(2)Cl(2)] (cisplatin) >> [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2) > Rh(2)(O(2)CCH(3))(4) approximately Pt(C(6)H(6)O(4))(NH(3))(2) (carboplatin). The relative reactivity of the complexes is associated with the lability of the leaving groups. The general trend is that an increase in the length of the oligonucleotide leads to enhanced reactivity for Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2) and Rh(2)(O(2)CCH(3))(4) (except for the case of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+), which reacts faster with the GG octamers than with the dodecamers), whereas the reactivity of Rh(2)(O(2)CCF(3))(4) is independent of the oligonucleotide length. When monitored by ESI, the dodecamers containing GG react faster than the respectiveAA oligonucleotides in reactions with Rh(2)(O(2)CCF(3))(4) and Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2), whereas AA oligonucleotides react faster with Rh(2)(O(2)CCH(3))(4). The mixed (AG, GA) purine sequences exhibit comparable rates of reactivity with the homopurine (AA, GG) dodecamers in reactions with Rh(2)(O(2)CCH(3))(4). The observation of initial dirhodium-DNA adducts with weak axial (ax) interactions, followed by rearrangement to more stable equatorial (eq) adducts, was achieved by electrospray ionization; the Rh-Rh bond as well as coordinated acetate or acetonitrile ligands remain intact in these dirhodium-DNA adducts. MALDI in-source decay (ISD), collision-induced dissociation (CID) MS-MS, and enzymatic digestion studies followed by MALDI and ESI MS reveal that, in the dirhodium compounds studied, the purine sites of the DNA oligonucleotides interact with the dirhodium core. Ultimately, both MALDI and ESI MS proved to be complementary, valuable tools for probing the identity and stability of dinuclear metal-DNA adducts.

Binding Sites↗

PubMed2004

Peptidomics of CNS-associated neurohemal systems of adult Drosophila melanogaster: a mass spectrometric survey of peptides from individual flies.

Neuropeptides are important messenger molecules that influence nearly all physiological processes. In insects, they can be released as neuromodulators within the central nervous system (CNS) or as neurohormones into the hemolymph. We analyzed the peptidome of neurohormonal release sites and associated secretory peptidergic neurons of adult Drosophila melanogaster. MALDI-TOF mass spectrometric analyzes were performed on single organs or cell cluster from individual flies. This first peptidomic characterization in adult fruit flies revealed 32 different neuropeptides. Peptides not directly predictable from previously cloned or annotated precursor genes were sequenced by tandem mass spectrometry. These peptides turned out to be either intermediate products of neuropeptide processing or shorter versions of known peptides. We found that the peptidome of the CNS-associated neurohemal organs is tagma-specific in Drosophila. Abdominal neurohemal organs and their supplying peptidergic neurons contain the capa gene products periviscerokinins and pyrokinin-1, thoracic neurohemal organs contain FMRFamides, and the neurohemal release sites of the brain contain pyrokinin-1(2-15), pyrokinin-2, corazonin, myosuppressin, and sNPF as their major putative release products. Our results show that peptidomic approaches are well suited to study differential neuropeptide expression or posttranslational modifications in morphologically defined parts of the nervous system and in a developmental and physiological context in animals as small as Drosophila melanogaster.

Animals↗

PubMed2004

Trafficking of ODV-E66 is mediated via a sorting motif and other viral proteins: facilitated trafficking to the inner nuclear membrane.

The N-terminal 33 aa of the envelope protein ODV-E66 are sufficient to traffic fusion proteins to intranuclear membranes and the ODV envelope during infection with Autographa californica nucleopolyhedrovirus. This sequence has two distinct features: (i) an extremely hydrophobic sequence of 18 aa and (ii) positively charged amino acids close to the C-terminal end of the hydrophobic sequence. In the absence of infection, this sequence is sufficient to promote protein accumulation at the inner nuclear membrane. Covalent cross-linking results show that the lysines of the motif are proximal to FP25K and/or BV/ODV-E26 during transit from the endoplasmic reticulum to the nuclear envelope. We propose that the 33 aa comprise a signature for sorting proteins to the inner nuclear membrane (sorting motif) and that, unlike other resident proteins of the inner nuclear membrane, ODV-E66 and sortingmotif fusions do not randomly diffuse from their site of insertion at the endoplasmic reticulum to the nuclear envelope and viral-induced intranuclear membranes. Rather, during infection, trafficking is mediated by protein-protein interactions.

Amino Acid Sequence↗