Conformational spread drives the evolution of the calcium-calmodulin protein kinase II.

ABSTRACT: The calcium calmodulin (Ca²⁺/CaM) dependent protein kinase II (CaMKII) decodes Ca²⁺ frequency oscillations. The CaMKIIα isoform is predominantly expressed in the brain and has a central role in learning. I matched residue and organismal evolution with collective motions deduced from the atomic structure of the human CaMKIIα holoenzyme to learn how its ring architecture abets function. Protein dynamic simulations showed its peripheral kinase domains (KDs) are conformationally coupled via lateral spread along the central hub. The underlying β-sheet motions in the hub or association domain (AD) were deconvolved into dynamic couplings based on mutual information. They mapped onto a coevolved residue network to partition the AD into two distinct sectors. A second, energeti

SUBMITTER: Khan S 

PROVIDER: S-EPMC9120016 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature