التفاصيل البيبلوغرافية
| العنوان: |
Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH. |
| المؤلفون: |
Hwang, Theresa1, Parker, Sara S.2, Hill, Samantha M.2, Grant, Robert A.1, Ilunga, Meucci W.1, Sivaraman, Venkatesh1, Mouneimne, Ghassan2, Keating, Amy E.1,3 keating@mit.edu |
| المصدر: |
eLife. 1/25/2022, p1-21. 21p. |
| مصطلحات موضوعية: |
*PROLINE, *PROTEIN-protein interactions, *PROTEINS, *CANCER invasiveness, *PROTEOMICS, *MICROFILAMENT proteins |
| مستخلص: |
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 proteomederived 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-rich SLiMs use a noncanonical site on the EVH1 domain for binding and display a thermodynamic signature consistent with the two-motif chain engaging a single domain. We also found that photoreceptor cilium actin regulator (PCARE) uses an extended 23-residue region to obtain a higher affinity than any known ENAH EVH1-binding motif. Our screen provides a way to uncover the effects of proteomic context on motif-mediated binding, revealing diverse mechanisms of control over EVH1 interactions and establishing that SLiMs can't be fully understood outside of their native context. [ABSTRACT FROM AUTHOR] |
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