Contribution of charged and polar residues for the formation of the E1-E2 heterodimer from Hepatitis C virus

The transmembrane domains of the envelope glycoprotein E1 and E2 have crucial multifunctional roles in the biogenesis of hepatitis C virus. We have performed molecular dynamics simulations to investigate a structural model of the transmembrane segments of the E1-E2 heterodimer. The simulations suppo...

وصف كامل

التفاصيل البيبلوغرافية
الحاوية / القاعدة:Journal of Molecular Modeling
المؤلف الرئيسي: 2-s2.0-77958044535
التنسيق: مقال
اللغة:English
منشور في: 2010
الوصول للمادة أونلاين:https://www.scopus.com/inward/record.uri?eid=2-s2.0-77958044535&doi=10.1007%2fs00894-010-0672-1&partnerID=40&md5=b8ea41d16fe90997ad3cc1f50ee9537c
id Jusoh S.A.; Welsch C.; Siu S.W.I.; Böckmann R.A.; Helms V.
spelling Jusoh S.A.; Welsch C.; Siu S.W.I.; Böckmann R.A.; Helms V.
2-s2.0-77958044535
Contribution of charged and polar residues for the formation of the E1-E2 heterodimer from Hepatitis C virus
2010
Journal of Molecular Modeling
16
10
10.1007/s00894-010-0672-1
https://www.scopus.com/inward/record.uri?eid=2-s2.0-77958044535&doi=10.1007%2fs00894-010-0672-1&partnerID=40&md5=b8ea41d16fe90997ad3cc1f50ee9537c
The transmembrane domains of the envelope glycoprotein E1 and E2 have crucial multifunctional roles in the biogenesis of hepatitis C virus. We have performed molecular dynamics simulations to investigate a structural model of the transmembrane segments of the E1-E2 heterodimer. The simulations support the key role of the Lys370-Asp728 ion pair for mediating the E1-E2 heterodimerization. In comparison to these two residues, the simulation results also reveal the differential effect of the conserved Arg730 residue that has been observed in experimental studies. Furthermore, we discovered the formation of inter-helical hydrogen bonds via Asn367 that stabilize dimer formation. Simulations of single and double mutants further demonstrate the importance of the ion-pair and polar interactions between the interacting helix monomers. The conformation of the E1 fragment in the simulation of the E1-E2 heterodimer is in close agreement with an NMR structure of the E1 transmembrane segment. The proposed model of the E1-E2 heterodimer supports the postulated cooperative insertion of both helices by the translocon complex into the bilayer. © Springer-Verlag 2010.

9485023
English
Article
All Open Access; Green Open Access
author 2-s2.0-77958044535
spellingShingle 2-s2.0-77958044535
Contribution of charged and polar residues for the formation of the E1-E2 heterodimer from Hepatitis C virus
author_facet 2-s2.0-77958044535
author_sort 2-s2.0-77958044535
title Contribution of charged and polar residues for the formation of the E1-E2 heterodimer from Hepatitis C virus
title_short Contribution of charged and polar residues for the formation of the E1-E2 heterodimer from Hepatitis C virus
title_full Contribution of charged and polar residues for the formation of the E1-E2 heterodimer from Hepatitis C virus
title_fullStr Contribution of charged and polar residues for the formation of the E1-E2 heterodimer from Hepatitis C virus
title_full_unstemmed Contribution of charged and polar residues for the formation of the E1-E2 heterodimer from Hepatitis C virus
title_sort Contribution of charged and polar residues for the formation of the E1-E2 heterodimer from Hepatitis C virus
publishDate 2010
container_title Journal of Molecular Modeling
container_volume 16
container_issue 10
doi_str_mv 10.1007/s00894-010-0672-1
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-77958044535&doi=10.1007%2fs00894-010-0672-1&partnerID=40&md5=b8ea41d16fe90997ad3cc1f50ee9537c
description The transmembrane domains of the envelope glycoprotein E1 and E2 have crucial multifunctional roles in the biogenesis of hepatitis C virus. We have performed molecular dynamics simulations to investigate a structural model of the transmembrane segments of the E1-E2 heterodimer. The simulations support the key role of the Lys370-Asp728 ion pair for mediating the E1-E2 heterodimerization. In comparison to these two residues, the simulation results also reveal the differential effect of the conserved Arg730 residue that has been observed in experimental studies. Furthermore, we discovered the formation of inter-helical hydrogen bonds via Asn367 that stabilize dimer formation. Simulations of single and double mutants further demonstrate the importance of the ion-pair and polar interactions between the interacting helix monomers. The conformation of the E1 fragment in the simulation of the E1-E2 heterodimer is in close agreement with an NMR structure of the E1 transmembrane segment. The proposed model of the E1-E2 heterodimer supports the postulated cooperative insertion of both helices by the translocon complex into the bilayer. © Springer-Verlag 2010.
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issn 9485023
language English
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