Structural mobility of the monomeric C-terminal domain of the HIV-1 capsid protein.
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.
Alcaraz
Luis A
LA
Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche (Alicante), Spain.
Del Alamo
Marta
M
Mateu
Mauricio G
MG
Neira
José L
JL
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
D036022:Capsid Proteins; D010455:Peptides; D014364:Tryptophan; D000409:Alanine