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Structural and functional insights into the interaction between the Cas family scaffolding protein p130Cas and the focal adhesion-associated protein paxillin
- Source :
- The Journal of biological chemistry, vol 292, iss 44
- Publication Year :
- 2017
- Publisher :
- eScholarship, University of California, 2017.
-
Abstract
- The Cas family scaffolding protein p130Cas is a Src substrate localized in focal adhesions (FAs) and functions in integrin signaling to promote cell motility, invasion, proliferation, and survival. p130Cas targeting to FAs is essential for its tyrosine phosphorylation and downstream signaling. Although the N-terminal SH3 domain is important for p130Cas localization, it has also been reported that the C-terminal region is involved in p130Cas FA targeting. The C-terminal region of p130Cas or Cas family homology domain (CCHD) has been reported to adopt a structure similar to that of the focal adhesion kinase C-terminal focal adhesion-targeting domain. The mechanism by which the CCHD promotes FA targeting of p130Cas, however, remains unclear. In this study, using a calorimetry approach, we identified the first LD motif (LD1) of the FA-associated protein paxillin as the binding partner of the p130Cas CCHD (in a 1:1 stoichiometry with a Kd ∼4.2 μm) and elucidated the structure of the p130Cas CCHD in complex with the paxillin LD1 motif by X-ray crystallography. Of note, a comparison of the CCHD/LD1 complex with a previously solved structure of CCHD in complex with the SH2-containing protein NSP3 revealed that LD1 had almost identical positioning of key hydrophobic and acidic residues relative to NSP3. Because paxillin is one of the key scaffold molecules in FAs, we propose that the interaction between the p130Cas CCHD and the LD1 motif of paxillin plays an important role in p130Cas FA targeting.
- Subjects :
- Models, Molecular
0301 basic medicine
Scaffold protein
PTK2 protein tyrosine kinase 2 (PTK2) (focal adhesion kinase)
Protein Conformation
Amino Acid Motifs
Crystallography, X-Ray
Biochemistry
Medical and Health Sciences
SH3 domain
Mice
0302 clinical medicine
Protein structure
Models
Protein Interaction Mapping
2.1 Biological and endogenous factors
focal adhesion
Aetiology
Cancer
p130Cas
Crystallography
Protein Stability
Biological Sciences
Recombinant Proteins
Cell biology
030220 oncology & carcinogenesis
Crk-Associated Substrate Protein
Hydrophobic and Hydrophilic Interactions
Signal Transduction
Proto-oncogene tyrosine-protein kinase Src
Biochemistry & Molecular Biology
Integrin
Biology
Focal adhesion
Avian Proteins
03 medical and health sciences
Leucine
Animals
Protein Interaction Domains and Motifs
Molecular Biology
p130Cas/BCAR1
Paxillin
Structural Homology
X-ray crystallography
paxillin
Binding Sites
Protein
Molecular
Cell Biology
Peptide Fragments
Kinetics
nuclear magnetic resonance
030104 developmental biology
Amino Acid Substitution
Structural Homology, Protein
scaffold protein
Mutation
Chemical Sciences
biology.protein
X-Ray
BCAR1
Chickens
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry, vol 292, iss 44
- Accession number :
- edsair.doi.dedup.....5d1200685c8b007a447ec2a67b2fde60