How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4 [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 608.2 Inventions and patents
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2014
• Mô tả vật lý: Size: Article No. e01754 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 262158
• Chủ đề: 1. 60 applied life sciences

Tóm tắt

The Nef protein of HIV-1 downregulates the cell surface co-receptor CD4 by hijacking the clathrin adaptor complex AP-2. The structural basis for the hijacking of AP-2 by Nef is revealed by a 2.9 � crystal structure of Nef bound to the ? and ?2 subunits of AP-2. Nef binds to AP-2 via its central loop (residues 149-179) and its core. The determinants for Nef binding include residues that directly contact AP-2 and others that stabilize the binding-competent conformation of the central loop. Residues involved in both direct and indirect interactions are required for the binding of Nef to AP-2 and for downregulation of CD4. These results lead to a model for the docking of the full AP-2 tetramer to membranes as bound to Nef, such that the cytosolic tail of CD4 is situated to interact with its binding site on Nef.