Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH.

ABSTRACT: The human proteome is replete with short linear motifs (SLiMs) of four to six residues that are critical for protein-protein interactions, yet the importance of the sequence surrounding such motifs is underexplored. We devised a proteomic screen to examine the influence of SLiM sequence context on protein-protein interactions. Focusing on the EVH1 domain of human ENAH, an actin regulator that is highly expressed in invasive cancers, we screened 36-residue proteome-derived peptides and discovered new interaction partners of ENAH and diverse mechanisms by which context influences binding. A pocket on the ENAH EVH1 domain that has diverged from other Ena/VASP paralogs recognizes extended SLiMs and favors motif-flanking proline residues. Many high-affinity ENAH binders that contain two proline

SUBMITTER: Hwang T 

PROVIDER: S-EPMC8789275 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature