朊病毒蛋白结构受与膜的pH依赖性相互作用影响：模型系统研究

Prion protein structure is affected by pH-dependent interaction with membranes: a study in a model system.

作者信息

Re Francesca, Sesana Silvia, Barbiroli Alberto, Bonomi Francesco, Cazzaniga Emanuela, Lonati Elena, Bulbarelli Alessandra, Masserini Massimo

机构信息

Department of Experimental Medicine, University of Milano-Bicocca, via Cadore 48, Monza, Italy.

出版信息

FEBS Lett. 2008 Jan 23;582(2):215-20. doi: 10.1016/j.febslet.2007.12.003. Epub 2007 Dec 17.

DOI:10.1016/j.febslet.2007.12.003

PMID:18082145

Abstract

Interaction of full length recombinant hamster prion protein with liposomes mimicking lipid rafts or non-raft membrane regions was studied by circular dichroism, chemical cross-linking and sucrose gradient ultracentrifugation. At pH 7.0, the protein bound palmitoyloleoylphosphatidylcholine/cholesterol/sphingomyelin/monosialoganglioside GM1 (GM1) ganglioside liposomes but not palmitoyloleoylphosphatidylcholine alone (bound/free=0.33 and 0.01, respectively), maintaining the native alpha-helical structure and monomeric form. At pH 5.0, though still binding to quaternary mixtures, in particular GM1, the protein bound also to palmitoyloleoylphosphatidylcholine (bound/free 0.35) becoming unfolded and oligomeric. The pH-dependent interaction with raft or non-raft membranes might have implication in vivo, by stabilizing or destabilizing the protein.

摘要

通过圆二色性、化学交联和蔗糖梯度超速离心法研究了全长重组仓鼠朊病毒蛋白与模拟脂筏或非脂筏膜区域的脂质体之间的相互作用。在pH 7.0时，该蛋白与棕榈酰油酰磷脂酰胆碱/胆固醇/鞘磷脂/单唾液酸神经节苷脂GM1（GM1）神经节苷脂脂质体结合，但不与单独的棕榈酰油酰磷脂酰胆碱结合（结合/游离分别为0.33和0.01），维持天然α-螺旋结构和单体形式。在pH 5.0时，尽管该蛋白仍与四级混合物（特别是GM1）结合，但也与棕榈酰油酰磷脂酰胆碱结合（结合/游离为0.35），从而变得展开并形成寡聚体。与脂筏或非脂筏膜的pH依赖性相互作用可能通过稳定或破坏该蛋白而在体内具有重要意义。