| dc.contributor |
Massachusetts Institute of Technology. Department of Biology |
|
| dc.creator |
Hwang, Theresa |
|
| dc.creator |
Parker, Sara S |
|
| dc.creator |
Hill, Samantha M |
|
| dc.creator |
Grant, Robert A |
|
| dc.creator |
Ilunga, Meucci W |
|
| dc.creator |
Sivaraman, Venkatesh |
|
| dc.creator |
Mouneimne, Ghassan |
|
| dc.creator |
Keating, Amy E |
|
| dc.date |
2022-12-12T19:17:32Z |
|
| dc.date |
2022-12-12T19:17:32Z |
|
| dc.date |
2022 |
|
| dc.date |
2022-12-12T19:12:21Z |
|
| dc.date.accessioned |
2023-03-01T18:07:31Z |
|
| dc.date.available |
2023-03-01T18:07:31Z |
|
| dc.identifier |
https://hdl.handle.net/1721.1/146850 |
|
| dc.identifier |
Hwang, Theresa, Parker, Sara S, Hill, Samantha M, Grant, Robert A, Ilunga, Meucci W et al. 2022. "Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH." eLife, 11. |
|
| dc.identifier.uri |
http://localhost:8080/xmlui/handle/CUHPOERS/278841 |
|
| dc.description |
<jats:p>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-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.</jats:p> |
|
| dc.format |
application/pdf |
|
| dc.language |
en |
|
| dc.publisher |
eLife Sciences Publications, Ltd |
|
| dc.relation |
10.7554/ELIFE.70680 |
|
| dc.relation |
eLife |
|
| dc.rights |
Creative Commons Attribution 4.0 International license |
|
| dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
|
| dc.source |
eLife |
|
| dc.title |
Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH |
|
| dc.type |
Article |
|
| dc.type |
http://purl.org/eprint/type/JournalArticle |
|