7PDF

focus refinement of soluble domain of adenylyl cyclase 9 in complex with Gs protein alpha subunit and MANT-GTP

7PDF の概要

• エントリーDOI: 10.2210/pdb7pdf/pdb
• EMDBエントリー: 13335 13336
• 分子名称: Adenylate cyclase 9, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: membrane protein, adenylyl cyclase, signalling transduction., signaling protein
• 由来する生物種: Bos taurus (cattle); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 198710.23

構造登録者

Qi, C.,Korkhov, V.M. (登録日: 2021-08-05, 公開日: 2022-01-26, 最終更新日: 2024-07-17)

主引用文献

Qi, C.,Lavriha, P.,Mehta, V.,Khanppnavar, B.,Mohammed, I.,Li, Y.,Lazaratos, M.,Schaefer, J.V.,Dreier, B.,Pluckthun, A.,Bondar, A.N.,Dessauer, C.W.,Korkhov, V.M.
Structural basis of adenylyl cyclase 9 activation.
Nat Commun, 13:1045-1045, 2022

PubMed Abstract: Adenylyl cyclase 9 (AC9) is a membrane-bound enzyme that converts ATP into cAMP. The enzyme is weakly activated by forskolin, fully activated by the G protein Gαs subunit and is autoinhibited by the AC9 C-terminus. Although our recent structural studies of the AC9-Gαs complex provided the framework for understanding AC9 autoinhibition, the conformational changes that AC9 undergoes in response to activator binding remains poorly understood. Here, we present the cryo-EM structures of AC9 in several distinct states: (i) AC9 bound to a nucleotide inhibitor MANT-GTP, (ii) bound to an artificial activator (DARPin C4) and MANT-GTP, (iii) bound to DARPin C4 and a nucleotide analogue ATPαS, (iv) bound to Gαs and MANT-GTP. The artificial activator DARPin C4 partially activates AC9 by binding at a site that overlaps with the Gαs binding site. Together with the previously observed occluded and forskolin-bound conformations, structural comparisons of AC9 in the four conformations described here show that secondary structure rearrangements in the region surrounding the forskolin binding site are essential for AC9 activation.

PubMed: 35210418
DOI: 10.1038/s41467-022-28685-y

実験手法

ELECTRON MICROSCOPY (3.8 Å)