4AY9

Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor

4AY9 の概要

• エントリーDOI: 10.2210/pdb4ay9/pdb
• 関連するPDBエントリー: 1FL7 1XUN 1XWD
• 分子名称: GLYCOPROTEIN HORMONES, ALPHA POLYPEPTIDE, FOLLITROPIN SUBUNIT BETA, FOLLICLE-STIMULATING HORMONE RECEPTOR, ... (5 entities in total)
• 機能のキーワード: hormone-receptor complex, leucine-rich repeats, lrr, gpcr, hormone/receptor
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 191566.22

構造登録者

Jiang, X.,Liu, H.,Chen, X.,He, X. (登録日: 2012-06-19, 公開日: 2012-08-08, 最終更新日: 2024-10-23)

主引用文献

Jiang, X.,Liu, H.,Chen, X.,Chen, P.,Fischer, D.,Sriraman, V.,Yu, H.N.,Arkinstall, S.,He, X.
Structure of Follicle-Stimulating Hormone in Complex with the Entire Ectodomain of its Receptor.
Proc.Natl.Acad.Sci.USA, 109:12491-, 2012

PubMed Abstract: FSH, a glycoprotein hormone, and the FSH receptor (FSHR), a G protein-coupled receptor, play central roles in human reproduction. We report the crystal structure of FSH in complex with the entire extracellular domain of FSHR (FSHR(ED)), including the enigmatic hinge region that is responsible for signal specificity. Surprisingly, the hinge region does not form a separate structural unit as widely anticipated but is part of the integral structure of FSHR(ED). In addition to the known hormone-binding site, FSHR(ED) provides interaction sites with the hormone: a sulfotyrosine (sTyr) site in the hinge region consistent with previous studies and a potential exosite resulting from putative receptor trimerization. Our structure, in comparison to others, suggests FSHR interacts with its ligand in two steps: ligand recruitment followed by sTyr recognition. FSH first binds to the high-affinity hormone-binding subdomain of FSHR and reshapes the ligand conformation to form a sTyr-binding pocket. FSHR then inserts its sTyr (i.e., sulfated Tyr335) into the FSH nascent pocket, eventually leading to receptor activation.

PubMed: 22802634
DOI: 10.1073/PNAS.1206643109

実験手法

X-RAY DIFFRACTION (2.5 Å)