Nature:CD36清道夫蛋白的結構

CD36超級家族中的清道夫受體蛋白調控脂質代謝和先天免疫。它們識別正常的和改性的脂蛋白及與病原體相關的分子模式。

在這項研究中，Sergio Grinstein及同事發表了對CD36家族蛋白LIMP-2 (lysosomal integral membrane protein type 2)所做的首次高解析度結構分析，同時通過同源模擬還發表了另外兩個超級家族成員SR-BI 和 CD36的結構。

該結構顯示存在一個橫貫該分子整個長度的大空腔，它可能起一個隧道的作用，膽固醇通過它被從所結合的脂蛋白輸送到胞質膜的外葉。（生物谷Bioon.com）

生物谷推薦的英文摘要

Nature           doi:10.1038/nature12684

Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36

Dante Neculai，Michael Schwake，Mani Ravichandran，Friederike Zunke，Richard F. Collins，Judith Peters，Mirela Neculai，Jonathan Plumb，Peter Loppnau，Juan Carlos Pizarro，Alma Seitova，William S. Trimble，Paul Saftig，Sergio Grinstein& Sirano Dhe-Paganon

Members of the CD36 superfamily of scavenger receptor proteins are important regulators of lipid metabolism and innate immunity. They recognize normal and modified lipoproteins， as well as pathogen-associated molecular patterns. The family consists of three members： SR-BI (which delivers cholesterol to the liver and steroidogenic organs and is a co-receptor for hepatitis C virus)， LIMP-2/LGP85 (which mediates lysosomal delivery of β-glucocerebrosidase and serves as a receptor for enterovirus 71 and coxsackieviruses) and CD36 (a fatty-acid transporter and receptor for phagocytosis of effete cells and Plasmodium-infected erythrocytes). Notably， CD36 is also a receptor for modified lipoproteins and β-amyloid， and has been implicated in the pathogenesis of atherosclerosis and of Alzheimer’s disease1. Despite their prominent roles in health and disease， understanding the function and abnormalities of the CD36 family members has been hampered by the paucity of information about their structure. Here we determine the crystal structure of LIMP-2 and infer， by homology modelling， the structure of SR-BI and CD36. LIMP-2 shows a helical bundle where β-glucocerebrosidase binds， and where ligands are most likely to bind to SR-BI and CD36. Remarkably， the crystal structure also shows the existence of a large cavity that traverses the entire length of the molecule. Mutagenesis of SR-BI indicates that the cavity serves as a tunnel through which cholesterol(esters) are delivered from the bound lipoprotein to the outer leaflet of the plasma membrane. We provide evidence supporting a model2 whereby lipidic constituents of the ligands attached to the receptor surface are handed off to the membrane through the tunnel， accounting for the selective lipid transfer characteristic of SR-BI and CD36.