6VC8
Crystal structure of wild-type KRAS4b(1-169) in complex with GMPPNP and Mg ion
Summary for 6VC8
| Entry DOI | 10.2210/pdb6vc8/pdb |
| Descriptor | GTPase KRas, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | kras, ras, kras4b, oncoprotein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 3 |
| Total formula weight | 59625.94 |
| Authors | Tran, T.H.,Davies, D.R.,Edwards, T.E.,Simanshu, D.K. (deposition date: 2019-12-20, release date: 2021-02-10, Last modification date: 2023-10-11) |
| Primary citation | 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 Cited by 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: 34983849DOI: 10.1073/pnas.2113297119 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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