Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / membrane docking / pronephric nephron development / cotranslational protein targeting to membrane / Ssh1 translocon complex / Sec61 translocon complex / protein targeting to ER / protein insertion into ER membrane / signal sequence binding / SRP-dependent cotranslational protein targeting to membrane, translocation ...Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / membrane docking / pronephric nephron development / cotranslational protein targeting to membrane / Ssh1 translocon complex / Sec61 translocon complex / protein targeting to ER / protein insertion into ER membrane / signal sequence binding / SRP-dependent cotranslational protein targeting to membrane, translocation / post-translational protein targeting to membrane, translocation / protein transmembrane transporter activity / phospholipid binding / ribosome binding / endoplasmic reticulum membrane 類似検索 - 分子機能
Protein translocase SEC61 complex, gamma subunit / Protein translocase SecE domain superfamily / Translocon Sec61/SecY, plug domain / Plug domain of Sec61p / Protein secE/sec61-gamma signature. / Protein secY signature 1. / Protein secY signature 2. / SecE/Sec61-gamma subunits of protein translocation complex / Protein translocase complex, SecE/Sec61-gamma subunit / SecY/SEC61-alpha family ...Protein translocase SEC61 complex, gamma subunit / Protein translocase SecE domain superfamily / Translocon Sec61/SecY, plug domain / Plug domain of Sec61p / Protein secE/sec61-gamma signature. / Protein secY signature 1. / Protein secY signature 2. / SecE/Sec61-gamma subunits of protein translocation complex / Protein translocase complex, SecE/Sec61-gamma subunit / SecY/SEC61-alpha family / SecY domain superfamily / SecY conserved site / SecY 類似検索 - ドメイン・相同性
Chem-Q6B / Protein transport protein Sec61 subunit alpha isoform 1 / Protein transport protein Sec61 subunit gamma 類似検索 - 構成要素
ジャーナル: Mol Cell / 年: 2020 タイトル: Structure of the Inhibited State of the Sec Translocon. 著者: Samuel F Gérard / Belinda S Hall / Afroditi M Zaki / Katherine A Corfield / Peter U Mayerhofer / Catia Costa / Daniel K Whelligan / Philip C Biggin / Rachel E Simmonds / Matthew K Higgins / 要旨: Protein secretion in eukaryotes and prokaryotes involves a universally conserved protein translocation channel formed by the Sec61 complex. Unrelated small-molecule natural products and synthetic ...Protein secretion in eukaryotes and prokaryotes involves a universally conserved protein translocation channel formed by the Sec61 complex. Unrelated small-molecule natural products and synthetic compounds inhibit Sec61 with differential effects for different substrates or for Sec61 from different organisms, making this a promising target for therapeutic intervention. To understand the mode of inhibition and provide insight into the molecular mechanism of this dynamic translocon, we determined the structure of mammalian Sec61 inhibited by the Mycobacterium ulcerans exotoxin mycolactone via electron cryo-microscopy. Unexpectedly, the conformation of inhibited Sec61 is optimal for substrate engagement, with mycolactone wedging open the cytosolic side of the lateral gate. The inability of mycolactone-inhibited Sec61 to effectively transport substrate proteins implies that signal peptides and transmembrane domains pass through the site occupied by mycolactone. This provides a foundation for understanding the molecular mechanism of Sec61 inhibitors and reveals novel features of translocon function and dynamics.
A: Protein transport protein Sec61 subunit alpha isoform 1 B: Protein transport protein Sec61 subunit gamma C: Protein transport protein Sec61 subunit beta ヘテロ分子