5WDR

Choanoflagellate Salpingoeca rosetta Ras with GMP-PNP

5WDR の概要

• エントリーDOI: 10.2210/pdb5wdr/pdb
• 分子名称: Ras protein, MAGNESIUM ION, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: small g-protein, gtpase, oncoprotein, hydrolase
• 由来する生物種: Salpingoeca rosetta
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40154.84

構造登録者

Kondo, Y.,Gee, C.L.,Kuriyan, J. (登録日: 2017-07-05, 公開日: 2017-07-19, 最終更新日: 2023-10-04)

主引用文献

Bandaru, P.,Shah, N.H.,Bhattacharyya, M.,Barton, J.P.,Kondo, Y.,Cofsky, J.C.,Gee, C.L.,Chakraborty, A.K.,Kortemme, T.,Ranganathan, R.,Kuriyan, J.
Deconstruction of the Ras switching cycle through saturation mutagenesis.
Elife, 6:-, 2017

PubMed Abstract: Ras proteins are highly conserved signaling molecules that exhibit regulated, nucleotide-dependent switching between active and inactive states. The high conservation of Ras requires mechanistic explanation, especially given the general mutational tolerance of proteins. Here, we use deep mutational scanning, biochemical analysis and molecular simulations to understand constraints on Ras sequence. Ras exhibits global sensitivity to mutation when regulated by a GTPase activating protein and a nucleotide exchange factor. Removing the regulators shifts the distribution of mutational effects to be largely neutral, and reveals hotspots of activating mutations in residues that restrain Ras dynamics and promote the inactive state. Evolutionary analysis, combined with structural and mutational data, argue that Ras has co-evolved with its regulators in the vertebrate lineage. Overall, our results show that sequence conservation in Ras depends strongly on the biochemical network in which it operates, providing a framework for understanding the origin of global selection pressures on proteins.

PubMed: 28686159
DOI: 10.7554/eLife.27810

実験手法

X-RAY DIFFRACTION (1.6 Å)