6VC8

Crystal structure of wild-type KRAS4b(1-169) in complex with GMPPNP and Mg ion

6VC8 の概要

• エントリーDOI: 10.2210/pdb6vc8/pdb
• 分子名称: GTPase KRas, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: kras, ras, kras4b, oncoprotein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 59625.94

構造登録者

Tran, T.H.,Davies, D.R.,Edwards, T.E.,Simanshu, D.K. (登録日: 2019-12-20, 公開日: 2021-02-10, 最終更新日: 2023-10-11)

主引用文献

Ingolfsson, H.I.,Neale, C.,Carpenter, T.S.,Shrestha, R.,Lopez, C.A.,Tran, T.H.,Oppelstrup, T.,Bhatia, H.,Stanton, L.G.,Zhang, X.,Sundram, S.,Di Natale, F.,Agarwal, A.,Dharuman, G.,Kokkila Schumacher, S.I.L.,Turbyville, T.,Gulten, G.,Van, Q.N.,Goswami, D.,Jean-Francois, F.,Agamasu, C.,Hettige, J.J.,Travers, T.,Sarkar, S.,Surh, M.P.,Yang, Y.,Moody, A.,Liu, S.,Van Essen, B.C.,Voter, A.F.,Ramanathan, A.,Hengartner, N.W.,Simanshu, D.K.,Stephen, A.G.,Bremer, P.T.,Gnanakaran, S.,Glosli, J.N.,Lightstone, F.C.,McCormick, F.,Nissley, D.V.,Streitz, F.H.
Machine learning-driven multiscale modeling reveals lipid-dependent dynamics of RAS signaling proteins.
Proc.Natl.Acad.Sci.USA, 119:-, 2022

PubMed Abstract: RAS is a signaling protein associated with the cell membrane that is mutated in up to 30% of human cancers. RAS signaling has been proposed to be regulated by dynamic heterogeneity of the cell membrane. Investigating such a mechanism requires near-atomistic detail at macroscopic temporal and spatial scales, which is not possible with conventional computational or experimental techniques. We demonstrate here a multiscale simulation infrastructure that uses machine learning to create a scale-bridging ensemble of over 100,000 simulations of active wild-type KRAS on a complex, asymmetric membrane. Initialized and validated with experimental data (including a new structure of active wild-type KRAS), these simulations represent a substantial advance in the ability to characterize RAS-membrane biology. We report distinctive patterns of local lipid composition that correlate with interfacially promiscuous RAS multimerization. These lipid fingerprints are coupled to RAS dynamics, predicted to influence effector binding, and therefore may be a mechanism for regulating cell signaling cascades.

PubMed: 34983849
DOI: 10.1073/pnas.2113297119

実験手法

X-RAY DIFFRACTION (2.5 Å)