Determinants of the HIV-1 core assembly pathway

Claudia S. López; Jacob D. Eccles; Amelia Still; Rachel E. Sloan; Robin Lid Barklis; Seyram M. Tsagli; Eric Barklis

doi:10.1016/j.virol.2011.05.011

Determinants of the HIV-1 core assembly pathway

Claudia S. López, Jacob D. Eccles, Amelia Still, Rachel E. Sloan, Robin Lid Barklis, Seyram M. Tsagli, Eric Barklis

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Based on structural information, we have analyzed the mechanism of mature HIV-1 core assembly and the contributions of structural elements to the assembly process. Through the use of several in vitro assembly assay systems, we have examined details of how capsid (CA) protein helix 1, ß-hairpin and cyclophilin loop elements impact assembly-dependent protein interactions, and we present evidence for a contribution of CA helix 6 to the mature assembly-competent conformation of CA. Additional experiments with mixtures of proteins in assembly reactions provide novel analyses of the mature core assembly mechanism. Our results support a model in which initial assembly products serve as scaffolds for further assembly by converting incoming subunits to assembly proficient conformations, while mutant subunits increase the probability of assembly termination events.

Original language	English (US)
Pages (from-to)	137-146
Number of pages	10
Journal	Virology
Volume	417
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2011.05.011
State	Published - Aug 15 2011

Keywords

Core assembly
Gag
Microscopy
Nucleation
Nucleocapsid
RNA
Retrovirus

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2011.05.011

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title = "Determinants of the HIV-1 core assembly pathway",

abstract = "Based on structural information, we have analyzed the mechanism of mature HIV-1 core assembly and the contributions of structural elements to the assembly process. Through the use of several in vitro assembly assay systems, we have examined details of how capsid (CA) protein helix 1, {\ss}-hairpin and cyclophilin loop elements impact assembly-dependent protein interactions, and we present evidence for a contribution of CA helix 6 to the mature assembly-competent conformation of CA. Additional experiments with mixtures of proteins in assembly reactions provide novel analyses of the mature core assembly mechanism. Our results support a model in which initial assembly products serve as scaffolds for further assembly by converting incoming subunits to assembly proficient conformations, while mutant subunits increase the probability of assembly termination events.",

keywords = "Core assembly, Gag, Microscopy, Nucleation, Nucleocapsid, RNA, Retrovirus",

author = "L{\'o}pez, {Claudia S.} and Eccles, {Jacob D.} and Amelia Still and Sloan, {Rachel E.} and Barklis, {Robin Lid} and Tsagli, {Seyram M.} and Eric Barklis",

note = "Funding Information: This research was supported by National Institutes of Health grants GM060170 and AI071798 to E.B and by the Collins Medical Trust to C.S.L. We also appreciate the help and support of Ayna Alfadhli, Henry McNett and Colleen Noviello.",

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doi = "10.1016/j.virol.2011.05.011",

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AU - López, Claudia S.

AU - Eccles, Jacob D.

AU - Still, Amelia

AU - Sloan, Rachel E.

AU - Barklis, Robin Lid

AU - Tsagli, Seyram M.

AU - Barklis, Eric

N1 - Funding Information: This research was supported by National Institutes of Health grants GM060170 and AI071798 to E.B and by the Collins Medical Trust to C.S.L. We also appreciate the help and support of Ayna Alfadhli, Henry McNett and Colleen Noviello.

PY - 2011/8/15

Y1 - 2011/8/15

N2 - Based on structural information, we have analyzed the mechanism of mature HIV-1 core assembly and the contributions of structural elements to the assembly process. Through the use of several in vitro assembly assay systems, we have examined details of how capsid (CA) protein helix 1, ß-hairpin and cyclophilin loop elements impact assembly-dependent protein interactions, and we present evidence for a contribution of CA helix 6 to the mature assembly-competent conformation of CA. Additional experiments with mixtures of proteins in assembly reactions provide novel analyses of the mature core assembly mechanism. Our results support a model in which initial assembly products serve as scaffolds for further assembly by converting incoming subunits to assembly proficient conformations, while mutant subunits increase the probability of assembly termination events.

AB - Based on structural information, we have analyzed the mechanism of mature HIV-1 core assembly and the contributions of structural elements to the assembly process. Through the use of several in vitro assembly assay systems, we have examined details of how capsid (CA) protein helix 1, ß-hairpin and cyclophilin loop elements impact assembly-dependent protein interactions, and we present evidence for a contribution of CA helix 6 to the mature assembly-competent conformation of CA. Additional experiments with mixtures of proteins in assembly reactions provide novel analyses of the mature core assembly mechanism. Our results support a model in which initial assembly products serve as scaffolds for further assembly by converting incoming subunits to assembly proficient conformations, while mutant subunits increase the probability of assembly termination events.

KW - Core assembly

KW - Gag

KW - Microscopy

KW - Nucleation

KW - Nucleocapsid

KW - RNA

KW - Retrovirus

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Determinants of the HIV-1 core assembly pathway

Abstract

Keywords

ASJC Scopus subject areas

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