This study presents the crystal structure of the N-terminal SH3 (SH3N) domain of growth factor receptor-bound protein 2 (Grb2) at 2.5 Å resolution. Grb2 is a small (215-amino-acid) adaptor protein that is widely expressed and involved in signal transduction/cell communication. The crystal structure of full-length Grb2 has previously been reported (PDB entry 1gri). The structure of the isolated SH3N domain is consistent with the full-length structure. The structure of the isolated SH3N domain was solved at a higher resolution (2.5 Å compared with 3.1 Å for the previously deposited structure) and made it possible to resolve some of the loops that were missing in the full-length structure. In addition, interactions between the carboxy-terminal region of the SH3N domain and the Sos1-binding sites were observed in the structure of the isolated domain. Analysis of these interactions provided new information about the ligand-binding properties of the SH3N domain of Grb2.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278502 | PMC |
| http://dx.doi.org/10.1107/S2053230X20007232 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Crk proteins activate the Rap1 guanine nucleotide exchange factor C3G by segregated adaptor-dependent and -independent mechanisms.
Cell Commun Signal
February 2023
Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Salamanca, 37007, Salamanca, Spain.
Background: C3G is a guanine nucleotide exchange factor (GEF) that activates Rap1 to promote cell adhesion. Resting C3G is autoinhibited and the GEF activity is released by stimuli that signal through tyrosine kinases. C3G is activated by tyrosine phosphorylation and interaction with Crk adaptor proteins, whose expression is elevated in multiple human cancers.
View Article and Find Full Text PDFTermination of TCR-mediated activation signals is regulated by CrkII-dependent Cbl-mediated ubiquitination and degradation of C3G.
Immunobiology
March 2023
The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel. Electronic address:
Crk adaptor proteins are key players in signal transduction from multiple cell surface receptors, including the T cell antigen receptor (TCR). The involvement of CrkII in the early stages of T cell activation is well documented, but little is known about its role during the termination of the activation response. We substantiated findings showing that CrkII utilizes its SH3N and SH2 domains to constitutively associate with C3G and transiently with Cbl in resting and TCR/CD3-stimulated T cells, respectively.
View Article and Find Full Text PDFCrystal structure of the SH3 domain of growth factor receptor-bound protein 2.
Acta Crystallogr F Struct Biol Commun
June 2020
Laboratory of Molecular Neurodegeneration, Institute of Biomedical systems and Biotechnologies, Peter the Great St Petersburg Polytechnic University, St Petersburg 194021, Russian Federation.
This study presents the crystal structure of the N-terminal SH3 (SH3N) domain of growth factor receptor-bound protein 2 (Grb2) at 2.5 Å resolution. Grb2 is a small (215-amino-acid) adaptor protein that is widely expressed and involved in signal transduction/cell communication.
View Article and Find Full Text PDFACAP4 interacts with CrkII to promote the recycling of integrin β1.
Biochem Biophys Res Commun
August 2019
School of Life Sciences, Anhui Medical University, Hefei, 230032, China. Electronic address:
ACAP4, a GTPase-activating protein (GAP) for the ADP-ribosylation factor 6 (ARF6), plays import roles in cell migration, cell polarity, vesicle trafficking and tumorigenesis. Similarly, the ubiquitously expressed adaptor protein CrkII functions in a wide range of cellular activities, including cell proliferation, T cell adhesion and activation, tumorigenesis, and bacterial pathogenesis. Here, we demonstrate that ACAP4 physically interacts with CrkII.
View Article and Find Full Text PDFThe Tumor Suppressor SASH1 Interacts With the Signal Adaptor CRKL to Inhibit Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer.
Cell Mol Gastroenterol Hepatol
April 2019
Department of Surgery, Technical University of Munich, School of Medicine, Klinikum Rechts der Isar, Munich, Germany. Electronic address:
Article Synopsis
- SASH1 is a tumor-suppressor gene that plays a crucial role in preventing metastasis in colorectal cancer, particularly with its loss linked to the spread of the disease.
- The study involved manipulating SASH1 levels in colon cancer cells using advanced genetic techniques, enabling researchers to observe changes in cell behavior related to metastasis and resistance to chemotherapy.
- Results indicated that lower SASH1 levels promote a process called epithelial-mesenchymal transition (EMT), leading to more invasive cancer traits, while SASH1 interacts with the oncoprotein CRKL to inhibit pathways necessary for EMT, reducing the potential for metastasis.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!