The structural basis of BCR-ABL recruitment of GRB2 in chronic myelogenous leukemia.

ABSTRACT: BCR-ABL drives chronic myeloid leukemia (CML). BCR binding to GRB2 transduces signaling via the Ras/MAPK pathway. Despite considerable data confirming the binding, molecular-level understanding of exactly how the two proteins interact, and, especially, what are the determinants of the specificity of the SH2^GRB2 domain-phosphorylated BCR (pBCR) recognition are still open questions. Yet, this is vastly important for understanding binding selectivity, and for predicting the phosphorylated receptors, or peptides, that are likely to bind. Here, we uncover these determinants and ascertain to what extent they relate to the affinity of the interaction. Toward this end, we modeled the complexes of the pBCR and SH2^GRB2 and other pY/Y-peptide-SH2 complexes and compared their spe

SUBMITTER: Liu Y 

PROVIDER: S-EPMC9279350 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature