New targets and designed inhibitors of ASAP Arf-GAPs derived from structural characterization of the ASAP1/440-kD ankyrin-B interaction.

ABSTRACT: ASAP1 and its paralog ASAP2 belong to a PI_4,5P₂-dependent Arf GTPase-activating protein (Arf-GAP) family capable of modulating membrane and cytoskeletal dynamics. ASAPs regulate cell adhesive structures such as invadosomes and focal adhesions during cell attachment and migration. Malfunctioning of ASAP1 has been implicated in the malignant phenotypes of various cancers. Here, we discovered that the SH3 domain of ASAP1 or ASAP2 specifically binds to a 12-residue, positively charged peptide fragment from the 440 kDa giant ankyrin-B, a neuronal axon specific scaffold protein. The high-resolution structure of the ASAP1-SH3 domain in complex with the gAnkB peptide revealed a noncanonical SH3-ligand binding mode with high affinity and specificity. Structural analysis of the

SUBMITTER: Li Y 

PROVIDER: S-EPMC11490884 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature