Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: Structural and mechanistic implications of p17 myristoylation
| العنوان: | Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: Structural and mechanistic implications of p17 myristoylation |
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| المؤلفون: | Jacek Lubkowski, Zhibin Wu, Bryan Ericksen, Wuyuan Lu, Jerry Alexandratos, Robert C. Gallo |
| المصدر: | Proceedings of the National Academy of Sciences. 101:11587-11592 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Protein Denaturation, Vesicle-associated membrane protein 8, Conformational change, HIV Antigens, Protein Conformation, viruses, Gene Products, gag, Biology, gag Gene Products, Human Immunodeficiency Virus, Viral Proteins, Protein structure, immune system diseases, Denaturation (biochemistry), Myristoylation, Multidisciplinary, Viral matrix protein, Myristates, Spectrum Analysis, Cell Membrane, virus diseases, Biological Sciences, Viral membrane, N-terminus, Biochemistry, Biophysics, Dimerization, Protein Binding |
| الوصف: | The HIV-1 matrix protein p17, excised proteolytically from the N terminus of the Gag polyprotein, forms a protective shell attached to the inner surface of the plasma membrane of the virus. During the late stages of the HIV-1 replication cycle, the N-terminally myristoylated p17 domain targets the Gag polyprotein to the host-cell membrane for particle assembly. In the early stages of HIV-1 replication, however, some p17 molecules dissociate from the viral membrane to direct the preintegration complex to the host-cell nucleus. These two opposing targeting functions of p17 require that the protein be capable of reversible membrane interaction. It is postulated that a significant structural change in p17 triggered by proteolytic cleavage of the Gag polyprotein sequesters the N-terminal myristoyl group, resulting in a weaker membrane binding by the matrix protein than the Gag precursor. To test this “myristoyl switch” hypothesis, we obtained highly purified synthetic HIV-1 p17 of 131 amino acid residues and its N-myristoylated form in large quantity. Both forms of p17 were characterized by circular dichroism spectroscopy, protein chemical denaturation, and analytical centrifugal sedimentation. Our results indicate that although N-myristoylation causes no spectroscopically discernible conformational change in p17, it stabilizes the protein by 1 kcal/mol and promotes protein trimerization in solution. These findings support the premise that the myristoyl switch in p17 is triggered not by a structural change associated with proteolysis, but rather by the destabilization of oligomeric structures of membrane-bound p17 in the absence of downstream Gag subdomains. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fdff0f3dee7140659286c7e1c3e09b98Test https://doi.org/10.1073/pnas.0404649101Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fdff0f3dee7140659286c7e1c3e09b98 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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