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Structural mobility of the monomeric C-terminal domain of the HIV-1 capsid protein.

Authors
  • Alcaraz, Luis A
  • Del Alamo, Marta
  • Mateu, Mauricio G
  • Neira, José L
Type
Published Article
Journal
The FEBS journal
Publication Date
Jul 01, 2008
Volume
275
Issue
13
Pages
3299–3311
Identifiers
DOI: 10.1111/j.1742-4658.2008.06478.x
PMID: 18489586
Source
Medline
License
Unknown

Abstract

The capsid protein of HIV-1 (p24) (CA) forms the mature capsid of the human immunodeficiency virus. Capsid assembly involves hexamerization of the N-terminal domain and dimerization of the C-terminal domain of CA (CAC), and both domains constitute potential targets for anti-HIV therapy. CAC homodimerization occurs mainly through its second helix, and it is abolished when its sole tryptophan is mutated to alanine. This mutant, CACW40A, resembles a transient monomeric intermediate formed during dimerization. Its tertiary structure is similar to that of the subunits in the dimeric, non-mutated CAC, but the segment corresponding to the second helix samples different conformations. The present study comprises a comprehensive examination of the CACW40A internal dynamics. The results obtained, with movements sampling a wide time regime (from pico- to milliseconds), demonstrate the high flexibility of the whole monomeric protein. The conformational exchange phenomena on the micro-to-millisecond time scale suggest a role for internal motions in the monomer-monomer interactions and, thus, flexibility of the polypeptide chain is likely to contribute to the ability of the protein to adopt different conformational states, depending on the biological environment.

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