Studies of the 'Chain Reversal Regions' of the Avian Sarcoma/Leukosis Virus (ASLV) and Ebolavirus Fusion Proteins: Analogous Residues Are Important, and a His Residue Unique to EnvA Affects the pH Dependence of ASLV Entry
| Autor: | Allissia Gilmartin, Judith M. White, Bonnie La, Sue E. Delos |
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| Rok vydání: | 2010 |
| Předmět: |
Protein Conformation
Stereochemistry Immunology Alpharetrovirus medicine.disease_cause Antiparallel (biochemistry) Microbiology Protein structure Viral Envelope Proteins Virology medicine Histidine Ebolavirus Coiled coil biology Hydrogen-Ion Concentration Virus Internalization biology.organism_classification Fusion protein Virus-Cell Interactions Avian sarcoma leukosis virus Biochemistry Insect Science Helix Viral Fusion Proteins |
| Zdroj: | Journal of Virology. 84:5687-5694 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Most class I fusion proteins exist as trimers of dimers composed of a receptor binding and a fusion subunit. In their postfusion forms, the three fusion subunits form trimers of hairpins consisting of a central coiled coil (formed by the N-terminal helices), an intervening sequence, and a region containing the C helix (and flanking strands) that runs antiparallel to and packs in the grooves of the N-terminal coiled coil. For filoviruses and most retroviruses, the intervening sequence includes a “chain reversal region” consisting of a short stretch of hydrophobic residues, a Gly-Gly pair, a CX 6 CC motif, and a bulky hydrophobic residue. Maerz and coworkers (A. L. Maerz, R. J. Center, B. E. Kemp, B. Kobe, and P. Poumbourios, J. Virol. 74: 6614-6621, 2000) proposed a model for this region of human T-cell leukemia virus type 1 (HTLV-1) Env in which expulsion of the final bulky hydrophobic residue is important for early conformational changes and specific residues in the chain reversal region are important for forming the final, stable trimer of hairpins. Here, we used mutagenesis and pseudovirus entry assays to test this model for the avian retrovirus avian sarcoma/leukosis virus (ASLV) and the filovirus ebolavirus Zaire. Our results are generally consistent with the model proposed for HTLV-1 Env. In addition, we show with ASLV EnvA that the bulky hydrophobic residue following the CX 6 CC motif is required for the step of prehairpin target membrane insertion, whereas other residues are required for the foldback step of fusion. We further found that a His residue that is unique to the chain reversal region of ASLV EnvA controls the pH at which ASLV entry occurs. |
| Databáze: | OpenAIRE |
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