التفاصيل البيبلوغرافية
| العنوان: |
Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH |
| المؤلفون: |
Hwang, Theresa, Parker, Sara S, Hill, Samantha M, Grant, Robert A, Ilunga, Meucci W, Sivaraman, Venkatesh, Mouneimne, Ghassan, Keating, Amy E |
| المساهمون: |
Massachusetts Institute of Technology. Department of Biology |
| المصدر: |
eLife |
| بيانات النشر: |
eLife Sciences Publications, Ltd |
| سنة النشر: |
2022 |
| المجموعة: |
DSpace@MIT (Massachusetts Institute of Technology) |
| الوصف: |
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. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
eLife; https://hdl.handle.net/1721.1/146850Test; 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. |
| الإتاحة: |
https://hdl.handle.net/1721.1/146850Test |
| حقوق: |
Creative Commons Attribution 4.0 International license ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.D165C16E |
| قاعدة البيانات: |
BASE |
