title: Structural mobility of the monomeric C-terminal domain of the HIV-1 capsid protein.
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.
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche (Alicante), Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Alcaraz
authors.forename: Marta
authors.initials: M
authors.lastname: Del Alamo
authors.forename: Mauricio G
authors.initials: MG
authors.lastname: Mateu
authors.forename: José L
authors.initials: JL
authors.lastname: Neira
mesh_terms: D000409:Alanine / Q000737:chemistry; D001671:Biochemistry / Q000379:methods; D036022:Capsid Proteins / Q000737:chemistry / Q000502:physiology*; D019281:Dimerization; D015497:HIV-1 / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014364:Tryptophan / Q000737:chemistry
chemical_list: D036022:Capsid Proteins; D010455:Peptides; D014364:Tryptophan; D000409:Alanine