5FTL

Cryo-EM structure of human p97 bound to ATPgS (Conformation I)

5FTL の概要

• エントリーDOI: 10.2210/pdb5ftl/pdb
• 関連するPDBエントリー: 5FTJ 5FTK 5FTM 5FTN
• EMDBエントリー: 3297
• 分子名称: TRANSITIONAL ENDOPLASMIC RETICULUM ATPASE, ADENOSINE-5'-DIPHOSPHATE (2 entities in total)
• 機能のキーワード: hydrolase, single-particle, p97, aaa atpase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 541747.33

構造登録者

Banerjee, S.,Bartesaghi, A.,Merk, A.,Rao, P.,Bulfer, S.L.,Yan, Y.,Green, N.,Mroczkowski, B.,Neitz, R.J.,Wipf, P.,Falconieri, V.,Deshaies, R.J.,Milne, J.L.S.,Huryn, D.,Arkin, M.,Subramaniam, S. (登録日: 2016-01-14, 公開日: 2016-01-27, 最終更新日: 2024-05-08)

主引用文献

Banerjee, S.,Bartesaghi, A.,Merk, A.,Rao, P.,Bulfer, S.L.,Yan, Y.,Green, N.,Mroczkowski, B.,Neitz, R.J.,Wipf, P.,Falconieri, V.,Deshaies, R.J.,Milne, J.L.S.,Huryn, D.,Arkin, M.,Subramaniam, S.
2.3 A Resolution Cryo-Em Structure of Human P97 and Mechanism of Allosteric Inhibition
Science, 351:871-, 2016

PubMed Abstract: p97 is a hexameric AAA+ adenosine triphosphatase (ATPase) that is an attractive target for cancer drug development. We report cryo-electron microscopy (cryo-EM) structures for adenosine diphosphate (ADP)-bound, full-length, hexameric wild-type p97 in the presence and absence of an allosteric inhibitor at resolutions of 2.3 and 2.4 angstroms, respectively. We also report cryo-EM structures (at resolutions of ~3.3, 3.2, and 3.3 angstroms, respectively) for three distinct, coexisting functional states of p97 with occupancies of zero, one, or two molecules of adenosine 5'-O-(3-thiotriphosphate) (ATPγS) per protomer. A large corkscrew-like change in molecular architecture, coupled with upward displacement of the N-terminal domain, is observed only when ATPγS is bound to both the D1 and D2 domains of the protomer. These cryo-EM structures establish the sequence of nucleotide-driven structural changes in p97 at atomic resolution. They also enable elucidation of the binding mode of an allosteric small-molecule inhibitor to p97 and illustrate how inhibitor binding at the interface between the D1 and D2 domains prevents propagation of the conformational changes necessary for p97 function.

PubMed: 26822609
DOI: 10.1126/SCIENCE.AAD7974

実験手法

ELECTRON MICROSCOPY (3.3 Å)