1XTR

Structure of small GTPase human Rheb in complex with GppNHp

1XTR の概要

• エントリーDOI: 10.2210/pdb1xtr/pdb
• 関連するPDBエントリー: 1XTQ 1XTS
• 分子名称: GTP-binding protein Rheb, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: beta saddle, p-loop, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endomembrane system ; Lipid-anchor ; Cytoplasmic side : Q15382
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20787.56

構造登録者

Yu, Y.,Ding, J. (登録日: 2004-10-24, 公開日: 2005-03-08, 最終更新日: 2023-10-25)

主引用文献

Yu, Y.,Li, S.,Xu, X.,Li, Y.,Guan, K.,Arnold, E.,Ding, J.
Structural Basis for the Unique Biological Function of Small GTPase RHEB
J.Biol.Chem., 280:17093-17100, 2005

PubMed Abstract: The small GTPase Rheb displays unique biological and biochemical properties different from other small GTPases and functions as an important mediator between the tumor suppressor proteins TSC1 and TSC2 and the mammalian target of rapamycin to stimulate cell growth. We report here the three-dimensional structures of human Rheb in complexes with GDP, GTP, and GppNHp (5'-(beta,gamma-imide)triphosphate), which reveal novel structural features of Rheb and provide a molecular basis for its distinct properties. During GTP/GDP cycling, switch I of Rheb undergoes conformational change while switch II maintains a stable, unusually extended conformation, which is substantially different from the alpha-helical conformation seen in other small GTPases. The unique switch II conformation results in a displacement of Gln64 (equivalent to the catalytic Gln61 of Ras), making it incapable of participating in GTP hydrolysis and thus accounting for the low intrinsic GTPase activity of Rheb. This rearrangement also creates space to accommodate the side chain of Arg15, avoiding its steric hindrance with the catalytic residue and explaining its noninvolvement in GTP hydrolysis. Unlike Ras, the phosphate moiety of GTP in Rheb is shielded by the conserved Tyr35 of switch I, leading to the closure of the GTP-binding site, which appears to prohibit the insertion of a potential arginine finger from its GTPase-activating protein. Taking the genetic, biochemical, biological, and structural data together, we propose that Rheb forms a new group of the Ras/Rap subfamily and uses a novel GTP hydrolysis mechanism that utilizes Asn1643 of the tuberous sclerosis complex 2 GTPase-activating protein domain instead of Gln64 of Rheb as the catalytic residue.

PubMed: 15728574
DOI: 10.1074/jbc.M501253200

実験手法

X-RAY DIFFRACTION (2.65 Å)