Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 11, Pages 4353-4358Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0609477104
Keywords
Gag; major homology region; viral assembly
Categories
Funding
- NHLBI NIH HHS [T32 HL 076115, R01 HL035716, HL 035716, T32 HL076115, R37 HL035716] Funding Source: Medline
- NIAID NIH HHS [P30 AI060354] Funding Source: Medline
- NIGMS NIH HHS [GM 066516, R01 GM052504, GM 52504, GM 47467, P01 GM047467, R01 GM066516] Funding Source: Medline
Ask authors/readers for more resources
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 dinner 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available