4KSE

Crystal structure of a HIV p51 (219-230) deletion mutant

4KSE の概要

• エントリーDOI: 10.2210/pdb4kse/pdb
• 分子名称: HIV p51 subunit, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: p51 subunit, hiv, aids, transferase
• 由来する生物種: Human immunodeficiency virus type 1 group M subtype B (HIV-1)
• 細胞内の位置: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P04585
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48816.95

構造登録者

Zheng, X.,Mueller, G.A.,Derose, E.F.,Pedersen, L.C.,Gabel, S.A.,Cuneo, M.J.,Krahn, J.M.,London, R.E. (登録日: 2013-05-17, 公開日: 2014-08-13, 最終更新日: 2023-09-20)

主引用文献

Zheng, X.,Pedersen, L.C.,Gabel, S.A.,Mueller, G.A.,Cuneo, M.J.,DeRose, E.F.,Krahn, J.M.,London, R.E.
Selective unfolding of one Ribonuclease H domain of HIV reverse transcriptase is linked to homodimer formation.
Nucleic Acids Res., 42:5361-5377, 2014

PubMed Abstract: HIV-1 reverse transcriptase (RT), a critical enzyme of the HIV life cycle and an important drug target, undergoes complex and largely uncharacterized conformational rearrangements that underlie its asymmetric folding, dimerization and subunit-selective ribonuclease H domain (RH) proteolysis. In the present article we have used a combination of NMR spectroscopy, small angle X-ray scattering and X-ray crystallography to characterize the p51 and p66 monomers and the conformational maturation of the p66/p66' homodimer. The p66 monomer exists as a loosely structured molecule in which the fingers/palm/connection, thumb and RH substructures are connected by flexible (disordered) linking segments. The initially observed homodimer is asymmetric and includes two fully folded RH domains, while exhibiting other conformational features similar to that of the RT heterodimer. The RH' domain of the p66' subunit undergoes selective unfolding with time constant ∼6.5 h, consistent with destabilization due to residue transfer to the polymerase' domain on the p66' subunit. A simultaneous increase in the intensity of resonances near the random coil positions is characterized by a similar time constant. Consistent with the residue transfer hypothesis, a construct of the isolated RH domain lacking the two N-terminal residues is shown to exhibit reduced stability. These results demonstrate that RH' unfolding is coupled to homodimer formation.

PubMed: 24574528
DOI: 10.1093/nar/gku143

実験手法

X-RAY DIFFRACTION (2.677 Å)