Alok K Sharma, Jun Pei, Yue Yang, Marcin Dyba, Brian Smith, Dana Rabara, Erik Larsen, Felice C Lightstone, Dominic Esposito, Andrew G Stephen, Bin Wang, Pedro J Beltran, Eli Wallace, Dwight V Nissley, Frank McCormick, Anna E Maciag
Individual oncogenic KRAS mutants confer distinct differences in biochemical properties and signaling for reasons that are not well understood. KRAS activity is closely coupled to protein dynamics and is regulated through two interconverting conformations: state 1 (inactive, effector binding deficient), and state 2 (active, effector binding enabled). Here we use 31 P NMR to delineate the differences in state 1 and state 2 populations present in wild-type (WT) and common KRAS oncogenic mutants (G12C, G12D, G12V, G13D, and Q61L) bound to its natural substrate GTP or a commonly used nonhydrolyzable analogue GppNHp...
January 16, 2024: Journal of Biological Chemistry