4IDP

human atlastin-1 1-446, N440T, GppNHp

4IDP の概要

• エントリーDOI: 10.2210/pdb4idp/pdb
• 関連するPDBエントリー: 3Q5D 3Q5E 4IDN 4IDO 4IDQ
• 分子名称: Atlastin-1, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: gtpase, gtp/gdp binding, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Multi-pass membrane protein: Q8WXF7
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 209226.13

構造登録者

Byrnes, L.J.,Singh, A.,Szeto, K.,Benvin, N.M.,O'Donnell, J.P.,Zipfel, W.R.,Sondermann, H. (登録日: 2012-12-12, 公開日: 2013-01-09, 最終更新日: 2024-10-16)

主引用文献

Byrnes, L.J.,Singh, A.,Szeto, K.,Benvin, N.M.,O'Donnell, J.P.,Zipfel, W.R.,Sondermann, H.
Structural basis for conformational switching and GTP loading of the large G protein atlastin.
Embo J., 32:369-384, 2013

PubMed Abstract: Atlastin, a member of the dynamin superfamily, is known to catalyse homotypic membrane fusion in the smooth endoplasmic reticulum (ER). Recent studies of atlastin have elucidated key features about its structure and function; however, several mechanistic details, including the catalytic mechanism and GTP hydrolysis-driven conformational changes, are yet to be determined. Here, we present the crystal structures of atlastin-1 bound to GDP·AlF(4)(-) and GppNHp, uncovering an intramolecular arginine finger that stimulates GTP hydrolysis when correctly oriented through rearrangements within the G domain. Utilizing Förster Resonance Energy Transfer, we describe nucleotide binding and hydrolysis-driven conformational changes in atlastin and their sequence. Furthermore, we discovered a nucleotide exchange mechanism that is intrinsic to atlastin's N-terminal domains. Our results indicate that the cytoplasmic domain of atlastin acts as a tether and homotypic interactions are timed by GTP binding and hydrolysis. Perturbation of these mechanisms may be implicated in a group of atlastin-associated hereditary neurodegenerative diseases.

PubMed: 23334294
DOI: 10.1038/emboj.2012.353

実験手法

X-RAY DIFFRACTION (2.587 Å)