6M9W

Structure of Mg-free KRAS4b (2-169) bound to GDP with the switch-I in fully open conformation

6M9W の概要

• エントリーDOI: 10.2210/pdb6m9w/pdb
• 分子名称: GTPase KRas, GUANOSINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: kras, ras, mg, k-ras-4b, small gtpase, guanine nucleotide, oncoprotein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19697.87

構造登録者

Dharmaiah, S.,Tran, T.H.,Yan, W.,Simanshu, D.K. (登録日: 2018-08-24, 公開日: 2019-07-31, 最終更新日: 2023-10-11)

主引用文献

Dharmaiah, S.,Tran, T.H.,Messing, S.,Agamasu, C.,Gillette, W.K.,Yan, W.,Waybright, T.,Alexander, P.,Esposito, D.,Nissley, D.V.,McCormick, F.,Stephen, A.G.,Simanshu, D.K.
Structures of N-terminally processed KRAS provide insight into the role of N-acetylation.
Sci Rep, 9:10512-10512, 2019

PubMed Abstract: Although post-translational modification of the C-terminus of RAS has been studied extensively, little is known about N-terminal processing. Mass spectrometric characterization of KRAS expressed in mammalian cells showed cleavage of the initiator methionine (iMet) and N-acetylation of the nascent N-terminus. Interestingly, structural studies on GDP- and GMPPNP-bound KRAS lacking the iMet and N-acetylation resulted in Mg-free structures of KRAS with flexible N-termini. In the Mg-free KRAS-GDP structure, the flexible N-terminus causes conformational changes in the interswitch region resulting in a fully open conformation of switch I. In the Mg-free KRAS-GMPPNP structure, the flexible N-terminus causes conformational changes around residue A59 resulting in the loss of Mg and switch I in the inactive state 1 conformation. Structural studies on N-acetylated KRAS-GDP lacking the iMet revealed the presence of Mg and a conformation of switch regions also observed in the structure of GDP-bound unprocessed KRAS with the iMet. In the absence of the iMet, the N-acetyl group interacts with the central beta-sheet and stabilizes the N-terminus and the switch regions. These results suggest there is crosstalk between the N-terminus and the Mg binding site, and that N-acetylation plays an important role by stabilizing the N-terminus of RAS upon excision of the iMet.

PubMed: 31324887
DOI: 10.1038/s41598-019-46846-w

実験手法

X-RAY DIFFRACTION (1.5 Å)