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Domain-swapped dimerization of the HIV-1 capsid C-terminal domain.


ABSTRACT: Assembly of the HIV and other retroviruses is primarily driven by the oligomerization of the Gag polyprotein, the major viral structural protein capable of forming virus-like particles even in the absence of all other virally encoded components. Several critical determinants of Gag oligomerization are located in the C-terminal domain of the capsid protein (CA-CTD), which encompasses the most conserved segment in the highly variable Gag protein called the major homology region (MHR). The CA-CTD is thought to function as a dimerization module, although the existing model of CA-CTD dimerization does not readily explain why the conserved residues of the MHR are essential for retroviral assembly. Here we describe an x-ray structure of a distinct domain-swapped variant of the HIV-1 CA-CTD dimer stabilized by a single amino acid deletion. In the domain-swapped structure, the MHR-containing segment forms a major part of the dimerization interface, providing a structural mechanism for the enigmatic function of the MHR in HIV assembly. Our observations suggest that swapping of the MHR segments of adjacent Gag molecules may be a critical intermediate in retroviral assembly.

SUBMITTER: Ivanov D 

PROVIDER: S-EPMC1838606 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Domain-swapped dimerization of the HIV-1 capsid C-terminal domain.

Ivanov Dmitri D   Tsodikov Oleg V OV   Kasanov Jeremy J   Ellenberger Tom T   Wagner Gerhard G   Collins Tucker T  

Proceedings of the National Academy of Sciences of the United States of America 20070305 11


Assembly of the HIV and other retroviruses is primarily driven by the oligomerization of the Gag polyprotein, the major viral structural protein capable of forming virus-like particles even in the absence of all other virally encoded components. Several critical determinants of Gag oligomerization are located in the C-terminal domain of the capsid protein (CA-CTD), which encompasses the most conserved segment in the highly variable Gag protein called the major homology region (MHR). The CA-CTD i  ...[more]

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