4GZL

Crystal structure of RAC1 Q61L mutant

4GZL の概要

• エントリーDOI: 10.2210/pdb4gzl/pdb
• 関連するPDBエントリー: 3SBD 3SBE 3TH5 4GZM
• 分子名称: Ras-related C3 botulinum toxin substrate 1, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: rossmann fold, gtp binding, membrane, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Lipid-anchor; Cytoplasmic side (By similarity): P63000
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46591.24

構造登録者

Ha, B.H.,Boggon, T.J. (登録日: 2012-09-06, 公開日: 2012-12-12, 最終更新日: 2023-09-13)

主引用文献

Davis, M.J.,Ha, B.H.,Holman, E.C.,Halaban, R.,Schlessinger, J.,Boggon, T.J.
RAC1P29S is a spontaneously activating cancer-associated GTPase.
Proc.Natl.Acad.Sci.USA, 110:912-917, 2013

PubMed Abstract: RAC1 is a small, Ras-related GTPase that was recently reported to harbor a recurrent UV-induced signature mutation in melanoma, resulting in substitution of P29 to serine (RAC1(P29S)), ranking this the third most frequently occurring gain-of-function mutation in melanoma. Although the Ras family GTPases are mutated in about 30% of all cancers, mutations in the Rho family GTPases have rarely been observed. In this study, we demonstrate that unlike oncogenic Ras proteins, which are primarily activated by mutations that eliminate GTPase activity, the activated melanoma RAC1(P29S) protein maintains intrinsic GTP hydrolysis and is spontaneously activated by substantially increased inherent GDP/GTP nucleotide exchange. Determination and comparison of crystal structures for activated RAC1 GTPases suggest that RAC1(F28L)--a known spontaneously activated RAC1 mutant--and RAC1(P29S) are self-activated in distinct fashions. Moreover, the mechanism of RAC1(P29S) and RAC1(F28L) activation differs from the common oncogenic mutations found in Ras-like GTPases that abrogate GTP hydrolysis. The melanoma RAC1(P29S) gain-of-function point mutation therefore represents a previously undescribed class of cancer-related GTPase activity.

PubMed: 23284172
DOI: 10.1073/pnas.1220895110

実験手法

X-RAY DIFFRACTION (2 Å)