PDBsum entry 5ih2

Signaling protein

PDB id: 5ih2

Contents

Protein chains

58 a.a.

12 a.a.

Ligands

PEG

P4G ×2

Metals

_NA ×4

Waters ×181

PDB id:

5ih2

Name:

Signaling protein

Title:

Structure, thermodynamics, and the role of conformational dynamics in the interactions between the n-terminal sh3 domain of crkii and proline-rich motifs in cabl

Structure:

Adapter molecule crk. Chain: a, b. Fragment: unp residues 134-191. Synonym: proto-oncogenE C-crk,p38. Engineered: yes. Proline rich peptide. Chain: m, n. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: crk, crko. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Endothia gyrosa. Organism_taxid: 40263

Resolution:

1.80Å R-factor: 0.173 R-free: 0.243

Authors:

V.S.Bhatt,D.Zeng,I.Krieger,J.C.Sacchettini,J.-H.Cho

Key ref:

V.S.Bhatt et al. (2016). Binding Mechanism of the N-Terminal SH3 Domain of CrkII and Proline-Rich Motifs in cAbl. Biophys J, 110, 2630-2641. PubMed id: 27332121 DOI: 10.1016/j.bpj.2016.05.008

Date:

28-Feb-16 Release date: 29-Jun-16

Protein chains

Q64010  (CRK_MOUSE) -  Adapter molecule crk from Mus musculus

Seq: 304 a.a.

Struc: 58 a.a.

Protein chains

P00520  (ABL1_MOUSE) -  Tyrosine-protein kinase ABL1 from Mus musculus

Seq: 1123 a.a.

Struc: 11 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains M, N: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.bpj.2016.05.008

Biophys J 110:2630-2641 (2016)

PubMed id: 27332121

Binding Mechanism of the N-Terminal SH3 Domain of CrkII and Proline-Rich Motifs in cAbl.

V.S.Bhatt, D.Zeng, I.Krieger, J.C.Sacchettini, J.H.Cho.

ABSTRACT

The N-terminal Src homology 3 (nSH3) domain of a signaling adaptor protein, CT-10 regulator of kinase II (CrkII), recognizes proline-rich motifs (PRMs) of binding partners, such as cAbl kinase. The interaction between CrkII and cAbl kinase is involved in the regulation of cell spreading, microbial pathogenesis, and cancer metastasis. Here, we report the detailed biophysical characterizations of the interactions between the nSH3 domain of CrkII and PRMs in cAbl. We identified that the nSH3 domain of CrkII binds to three PRMs in cAbl with virtually identical affinities. Structural studies, by using x-ray crystallography and NMR spectroscopy, revealed that the binding modes of all three nSH3:PRM complexes are highly similar to each other. Van 't Hoff analysis revealed that nSH3:PRM interaction is associated with favorable enthalpy and unfavorable entropy change. The combination of experimentally determined thermodynamic parameters, structure-based calculations, and (15)N NMR relaxation analysis highlights the energetic contribution of conformational entropy change upon the complex formation, and water molecules structured in the binding interface of the nSH3:PRM complex. Understanding the molecular basis of nSH3:PRM interaction will provide, to our knowledge, new insights for the rational design of small molecules targeting the interaction between CrkII and cAbl.