Data‐driven model of the KRas4B/Calmodulin complex

KRas4B (henceforth called KRas) is a small GTPase that regulates activation of variety signaling pathways, including the Raf/MEK/ERK pathway, leading to cell proliferation, survival, and differentiation. Activation these pathways dependent on nucleotide-bound state KRas: GTP-bound KRas “turns on” while GDP-bound off” signaling. Interestingly, only one three Ras isoforms interacts with Ca2+-bound calmodulin (CaM). However, attempts crystallize KRas/CaM complex have proven difficult due flexible nature hypervariable region (HVR) as well linker CaM. We present model containing unprocessed full-length in CaM, guided by angle x-ray scattering (SAXS), NMR nuclear overhouser effects chemical shift perturbations. The low-resolution envelope shows CaM an open conformation. NOEs suggest HVR adopts helical conformation Our experimental data, together published perturbations lead fits our SAXS envelop (ꭓ=1.97). This will be refined using molecular dynamics simulations.