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Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode
SH3 domains are common protein binding modules. The target sequence of SH3 domains is usually a proline-rich motif (PRM) containing a minimal “PxxP” sequence. The mechanism of how different SH3 domains specifically choose their targets from vast PxxP-containing sequences is still not very clear, as...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865144/ https://www.ncbi.nlm.nih.gov/pubmed/36674928 http://dx.doi.org/10.3390/ijms24021414 |
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author | Jia, Xuanyan Lin, Leishu Xu, Shun Li, Lingxuan Wei, Zhiyi Yu, Cong Niu, Fengfeng |
author_facet | Jia, Xuanyan Lin, Leishu Xu, Shun Li, Lingxuan Wei, Zhiyi Yu, Cong Niu, Fengfeng |
author_sort | Jia, Xuanyan |
collection | PubMed |
description | SH3 domains are common protein binding modules. The target sequence of SH3 domains is usually a proline-rich motif (PRM) containing a minimal “PxxP” sequence. The mechanism of how different SH3 domains specifically choose their targets from vast PxxP-containing sequences is still not very clear, as many reported SH3/PRM interactions are weak and promiscuous. Here, we identified the binding of the SH3 domain of ASAP1 to the PRM of MICAL1 with a sub-μM binding affinity, and determined the crystal structure of ASAP1-SH3 and MICAL1-PRM complex. Our structural and biochemical analyses revealed that the target-binding pocket of ASAP1-SH3 contains two negatively charged patches to recognize the “xPx + Px+” sequence in MICAL1-PRM and consequently strengthen the interaction, differing from the typical SH3/PRM interaction. This unique PRM-binding pocket is also found in the SH3 domains of GTPase Regulator associated with focal adhesion kinase (GRAF) and Src kinase associated phosphoprotein 1 (SKAP1), which we named SH3(AGS). In addition, we searched the Swiss-Prot database and found ~130 proteins with the SH3(AGS)-binding PRM in silico. Finally, gene ontology analysis suggests that the strong interaction between the SH3(AGS)-containing proteins and their targets may play roles in actin cytoskeleton regulation and vesicle trafficking. |
format | Online Article Text |
id | pubmed-9865144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98651442023-01-22 Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode Jia, Xuanyan Lin, Leishu Xu, Shun Li, Lingxuan Wei, Zhiyi Yu, Cong Niu, Fengfeng Int J Mol Sci Article SH3 domains are common protein binding modules. The target sequence of SH3 domains is usually a proline-rich motif (PRM) containing a minimal “PxxP” sequence. The mechanism of how different SH3 domains specifically choose their targets from vast PxxP-containing sequences is still not very clear, as many reported SH3/PRM interactions are weak and promiscuous. Here, we identified the binding of the SH3 domain of ASAP1 to the PRM of MICAL1 with a sub-μM binding affinity, and determined the crystal structure of ASAP1-SH3 and MICAL1-PRM complex. Our structural and biochemical analyses revealed that the target-binding pocket of ASAP1-SH3 contains two negatively charged patches to recognize the “xPx + Px+” sequence in MICAL1-PRM and consequently strengthen the interaction, differing from the typical SH3/PRM interaction. This unique PRM-binding pocket is also found in the SH3 domains of GTPase Regulator associated with focal adhesion kinase (GRAF) and Src kinase associated phosphoprotein 1 (SKAP1), which we named SH3(AGS). In addition, we searched the Swiss-Prot database and found ~130 proteins with the SH3(AGS)-binding PRM in silico. Finally, gene ontology analysis suggests that the strong interaction between the SH3(AGS)-containing proteins and their targets may play roles in actin cytoskeleton regulation and vesicle trafficking. MDPI 2023-01-11 /pmc/articles/PMC9865144/ /pubmed/36674928 http://dx.doi.org/10.3390/ijms24021414 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jia, Xuanyan Lin, Leishu Xu, Shun Li, Lingxuan Wei, Zhiyi Yu, Cong Niu, Fengfeng Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode |
title | Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode |
title_full | Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode |
title_fullStr | Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode |
title_full_unstemmed | Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode |
title_short | Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode |
title_sort | crystal structure of the sh3 domain of asap1 in complex with the proline rich motif (prm) of mical1 reveals a unique sh3/prm interaction mode |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865144/ https://www.ncbi.nlm.nih.gov/pubmed/36674928 http://dx.doi.org/10.3390/ijms24021414 |
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