5KZB

Crystal structure of the Rous sarcoma virus matrix protein (aa 2-102). Space group I4122

5KZB の概要

• エントリーDOI: 10.2210/pdb5kzb/pdb
• 関連するPDBエントリー: 5KZ9 5KZA
• 分子名称: Virus Matrix Protein (2 entities in total)
• 機能のキーワード: viral protein; matrix protein; membrane associated protein, viral protein
• 由来する生物種: Rous sarcoma virus (strain Prague C) (RSV-PrC)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11089.86

構造登録者

Kingston, R.L.,Chan, J.,Vogt, V.M. (登録日: 2016-07-24, 公開日: 2017-07-26, 最終更新日: 2024-03-06)

主引用文献

Doktorova, M.,Heberle, F.A.,Kingston, R.L.,Khelashvili, G.,Cuendet, M.A.,Wen, Y.,Katsaras, J.,Feigenson, G.W.,Vogt, V.M.,Dick, R.A.
Cholesterol Promotes Protein Binding by Affecting Membrane Electrostatics and Solvation Properties.
Biophys. J., 113:2004-2015, 2017

PubMed Abstract: Binding of the retroviral structural protein Gag to the cellular plasma membrane is mediated by the protein's matrix (MA) domain. Prominent among MA-PM interactions is electrostatic attraction between the positively charged MA domain and the negatively charged plasma membrane inner leaflet. Previously, we reported that membrane association of HIV-1 Gag, as well as purified Rous sarcoma virus (RSV) MA and Gag, depends strongly on the presence of acidic lipids and is enhanced by cholesterol (Chol). The mechanism underlying this enhancement was unclear. Here, using a broad set of in vitro and in silico techniques we addressed molecular mechanisms of association between RSV MA and model membranes, and investigated how Chol enhances this association. In neutron scattering experiments with liposomes in the presence or absence of Chol, MA preferentially interacted with preexisting POPS-rich clusters formed by nonideal lipid mixing, binding peripherally to the lipid headgroups with minimal perturbation to the bilayer structure. Molecular dynamics simulations showed a stronger MA-bilayer interaction in the presence of Chol, and a large Chol-driven increase in lipid packing and membrane surface charge density. Although in vitro MA-liposome association is influenced by disparate variables, including ionic strength and concentrations of Chol and charged lipids, continuum electrostatic theory revealed an underlying dependence on membrane surface potential. Together, these results conclusively show that Chol affects RSV MA-membrane association by making the electrostatic potential at the membrane surface more negative, while decreasing the penalty for lipid headgroup desolvation. The presented approach can be applied to other viral and nonviral proteins.

PubMed: 29117524
DOI: 10.1016/j.bpj.2017.08.055

実験手法

X-RAY DIFFRACTION (3.2 Å)