Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 570 Life sciences Biology
• 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, 2015
• Mô tả vật lý: Size: p. 833-844 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261165
• Chủ đề: 1. 59 basic biological sciences; 2. 60 applied life sciences; 3. Anti-hypertensive drugs; 4. At1r

Tóm tắt

 We report that angiotensin II type 1 receptor (AT<
 sub>
 1<
 /sub>
 R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT<
 sub>
 1<
 /sub>
 R blockers (ARBs), the structural basis for AT<
 sub>
 1<
 /sub>
 R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT<
 sub>
 1<
 /sub>
 R in complex with its selective antagonist ZD7155 at 2.9 � resolution. The AT<
 sub>
 1<
 /sub>
 R-ZD7155 complex structure revealed key structural features ofAT<
 sub>
 1<
 /sub>
 R and critical interactions for ZD7155 binding. Finally, docking simulations of the clinically used ARBs into the AT<
 sub>
 1<
 /sub>
 R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT<
 sub>
 1<
 /sub>
 R structure-function relationship and structure-based drug design.