Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases.

ABSTRACT: Despite their apparent lack of catalytic activity, pseudokinases are essential signaling molecules. Here, we describe the structural and dynamic properties of pseudokinase domains from the Wnt-binding receptor tyrosine kinases (PTK7, ROR1, ROR2, and RYK), which play important roles in development. We determined structures of all pseudokinase domains in this family and found that they share a conserved inactive conformation in their activation loop that resembles the autoinhibited insulin receptor kinase (IRK). They also have inaccessible ATP-binding pockets, occluded by aromatic residues that mimic a cofactor-bound state. Structural comparisons revealed significant domain plasticity and alternative interactions that substitute for absent conserved motifs. The pseudokinases also showed dyna

SUBMITTER: Sheetz JB 

PROVIDER: S-EPMC7543951 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature