The Disordered Cellular Multi-Tasker WIP and Its Protein–Protein Interactions: A Structural View
WASp-interacting protein (WIP), a regulator of actin cytoskeleton assembly and remodeling, is a cellular multi-tasker and a key member of a network of protein–protein interactions, with significant impact on health and disease. Here, we attempt to complement the well-established understanding of WIP...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/7/1084 |
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| author | Chana G. Sokolik Nasrin Qassem Jordan H. Chill |
| author_facet | Chana G. Sokolik Nasrin Qassem Jordan H. Chill |
| author_sort | Chana G. Sokolik |
| collection | DOAJ |
| description | WASp-interacting protein (WIP), a regulator of actin cytoskeleton assembly and remodeling, is a cellular multi-tasker and a key member of a network of protein–protein interactions, with significant impact on health and disease. Here, we attempt to complement the well-established understanding of WIP function from cell biology studies, summarized in several reviews, with a structural description of WIP interactions, highlighting works that present a molecular view of WIP’s protein–protein interactions. This provides a deeper understanding of the mechanisms by which WIP mediates its biological functions. The fully disordered WIP also serves as an intriguing example of how intrinsically disordered proteins (IDPs) exert their function. WIP consists of consecutive small functional domains and motifs that interact with a host of cellular partners, with a striking preponderance of proline-rich motif capable of interactions with several well-recognized binding partners; indeed, over 30% of the WIP primary structure are proline residues. We focus on the binding motifs and binding interfaces of three important WIP segments, the actin-binding N-terminal domain, the central domain that binds SH3 domains of various interaction partners, and the WASp-binding C-terminal domain. Beyond the obvious importance of a more fundamental understanding of the biology of this central cellular player, this approach carries an immediate and highly beneficial effect on drug-design efforts targeting WIP and its binding partners. These factors make the value of such structural studies, challenging as they are, readily apparent. |
| first_indexed | 2024-03-10T18:20:24Z |
| format | Article |
| id | doaj.art-fab690a77f6540f994140b936aa77713 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T18:20:24Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-fab690a77f6540f994140b936aa777132023-11-20T07:25:45ZengMDPI AGBiomolecules2218-273X2020-07-01107108410.3390/biom10071084The Disordered Cellular Multi-Tasker WIP and Its Protein–Protein Interactions: A Structural ViewChana G. Sokolik0Nasrin Qassem1Jordan H. Chill2Department of Chemistry, Bar Ilan University, Ramat Gan 52900, IsraelDepartment of Chemistry, Bar Ilan University, Ramat Gan 52900, IsraelDepartment of Chemistry, Bar Ilan University, Ramat Gan 52900, IsraelWASp-interacting protein (WIP), a regulator of actin cytoskeleton assembly and remodeling, is a cellular multi-tasker and a key member of a network of protein–protein interactions, with significant impact on health and disease. Here, we attempt to complement the well-established understanding of WIP function from cell biology studies, summarized in several reviews, with a structural description of WIP interactions, highlighting works that present a molecular view of WIP’s protein–protein interactions. This provides a deeper understanding of the mechanisms by which WIP mediates its biological functions. The fully disordered WIP also serves as an intriguing example of how intrinsically disordered proteins (IDPs) exert their function. WIP consists of consecutive small functional domains and motifs that interact with a host of cellular partners, with a striking preponderance of proline-rich motif capable of interactions with several well-recognized binding partners; indeed, over 30% of the WIP primary structure are proline residues. We focus on the binding motifs and binding interfaces of three important WIP segments, the actin-binding N-terminal domain, the central domain that binds SH3 domains of various interaction partners, and the WASp-binding C-terminal domain. Beyond the obvious importance of a more fundamental understanding of the biology of this central cellular player, this approach carries an immediate and highly beneficial effect on drug-design efforts targeting WIP and its binding partners. These factors make the value of such structural studies, challenging as they are, readily apparent.https://www.mdpi.com/2218-273X/10/7/1084WASp interacting proteinprotein–protein interactionsintrinsically disordered proteinsactincytoskeleton remodelingSH3 domain |
| spellingShingle | Chana G. Sokolik Nasrin Qassem Jordan H. Chill The Disordered Cellular Multi-Tasker WIP and Its Protein–Protein Interactions: A Structural View Biomolecules WASp interacting protein protein–protein interactions intrinsically disordered proteins actin cytoskeleton remodeling SH3 domain |
| title | The Disordered Cellular Multi-Tasker WIP and Its Protein–Protein Interactions: A Structural View |
| title_full | The Disordered Cellular Multi-Tasker WIP and Its Protein–Protein Interactions: A Structural View |
| title_fullStr | The Disordered Cellular Multi-Tasker WIP and Its Protein–Protein Interactions: A Structural View |
| title_full_unstemmed | The Disordered Cellular Multi-Tasker WIP and Its Protein–Protein Interactions: A Structural View |
| title_short | The Disordered Cellular Multi-Tasker WIP and Its Protein–Protein Interactions: A Structural View |
| title_sort | disordered cellular multi tasker wip and its protein protein interactions a structural view |
| topic | WASp interacting protein protein–protein interactions intrinsically disordered proteins actin cytoskeleton remodeling SH3 domain |
| url | https://www.mdpi.com/2218-273X/10/7/1084 |
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