Related Experiment Video

Updated: Aug 18, 2026

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry
09:38

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry

Published on: June 26, 2019

The serine-rich domain from Crk-associated substrate (p130cas) is a four-helix bundle

Klára Briknarová1, Fariborz Nasertorabi, Marnie L Havert

  • 1Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.

The Journal of Biological Chemistry
|March 30, 2005
PubMed

Insights

The structure of a key domain in Crk-associated substrate (Cas) was determined, revealing a stable four-helix bundle. This finding provides insights into cell adhesion and signaling pathways, potentially impacting cancer research.

Area of Science:

  • Cell Biology
  • Structural Biology
  • Biochemistry

Background:

  • p130(cas) (Crk-associated substrate) is a crucial docking protein regulating cell adhesion, migration, survival, and proliferation.
  • It plays a significant role in both physiological processes and oncogenic transformation.
  • Cas contains multiple protein-protein interaction motifs, including a serine-rich region crucial for its function.

Purpose of the Study:

  • To determine the three-dimensional structure of the serine-rich functional domain of Cas.
  • To elucidate the structural basis for Cas interactions and its role in cellular signaling.
  • To identify potential regulatory sites within the Cas serine-rich domain.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy was employed to determine the solution structure of the Cas serine-rich region.
  • Site-directed mutagenesis and binding assays were utilized to characterize phosphorylation sites and interactions with 14-3-3 proteins.
  • Amino acid conservation analysis was performed on the molecular surface.

Main Results:

  • The serine-rich region of Cas was found to fold as a stable four-helix bundle, a known protein-interaction motif.
  • This structure exhibits significant similarity to four-helix bundles in other focal adhesion components like focal adhesion kinase, alpha-catenin, and vinculin.
  • Potential phosphorylation sites and a previously unidentified protein interaction site near the C terminus were identified.

Conclusions:

  • The Cas serine-rich region adopts a stable four-helix bundle structure, crucial for its function as a docking protein.
  • Structural similarities suggest conserved mechanisms of interaction within the focal adhesion complex.
  • The identified interaction sites offer new avenues for understanding Cas-mediated signaling in normal and pathological conditions, including cancer.

More Related Videos

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions06:50

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Published on: January 26, 2024

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells06:44

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

Published on: March 1, 2024

Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Cytoskeletal Linker Proteins - Plakins01:09

Cytoskeletal Linker Proteins - Plakins

Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...