Structures of N-terminally processed KRAS provide insight into the role of N-acetylation.

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 Mg²⁺-free structures of KRAS with flexible N-termini. In the Mg²⁺-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 Mg²⁺-free KRAS-GMPPNP structure, the flexible N-terminus causes conformational changes around residue A59 resulting

SUBMITTER: Dharmaiah S 

PROVIDER: S-EPMC6642148 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature