Interaction specificity of clustered protocadherins inferred from sequence covariation and structural analysis.

ABSTRACT: Clustered protocadherins, a large family of paralogous proteins that play important roles in neuronal development, provide an important case study of interaction specificity in a large eukaryotic protein family. A mammalian genome has more than 50 clustered protocadherin isoforms, which have remarkable homophilic specificity for interactions between cellular surfaces. A large antiparallel dimer interface formed by the first 4 extracellular cadherin (EC) domains controls this interaction. To understand how specificity is achieved between the numerous paralogs, we used a combination of structural and computational approaches. Molecular dynamics simulations revealed that individual EC interactions are weak and undergo binding and unbinding events, but together they form a stable complex throu

SUBMITTER: Nicoludis JM 

PROVIDER: S-EPMC6731663 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature