PDBsum entry 1ckb

Complex (oncogene protein/peptide)

PDB id

1ckb

Contents

			Protein chain

					57 a.a. *

			Ligands

					PRO-PRO-PRO-VAL- PRO-PRO-ARG-ARG

			Waters ×204

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structural basis for the specific interaction of lysine-Containing proline-Rich peptides with the n-Terminal sh3 domain of c-Crk.

Authors

X.Wu, B.Knudsen, S.M.Feller, J.Zheng, A.Sali, D.Cowburn, H.Hanafusa, J.Kuriyan.

Ref.

Structure, 1995, 3, 215-226. [DOI no: 10.1016/S0969-2126(01)00151-4]

PubMed id

7735837

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a perfect match.

Abstract

BACKGROUND: Proline-rich segments in the guanine nucleotide exchange factor C3G bind much more strongly to the N-terminal Src homology 3 domain (SH3-N) of the proto-oncogene product c-Crk than to other SH3 domains. The presence of a lysine instead of an arginine in the peptides derived from C3G appears to be crucial for this specificity towards c-Crk. RESULTS: In order to understand the chemical basis of this specificity we have determined the crystal structure of Crk SH3-N in complex with a high affinity peptide from C3G (PPPALPPKKR, Kd approximately 2 microM) at 1.5 A resolution. The peptide adopts a polyproline type II helix that binds, as dictated by electrostatic complementarity, in reversed orientation relative to the orientation seen in the earliest structures of SH3-peptide complexes. A lysine in the C3G peptide is tightly coordinated by three acidic residues in the SH3 domain. In contrast, the co-crystal structure of c-Crk SH3-N and a peptide containing an arginine at the equivalent position (determined at 1.9 A resolution) reveals non-optimal geometry for the arginine and increased disorder. CONCLUSIONS: The c-Crk SH3 domain engages in an unusual lysine-specific interaction that is rarely seen in protein structures, and which appears to be a key determinant of its unique ability to bind the C3G peptides with high affinity.



	Figure 3. Figure 3. Schematic diagram showing interactions between the C3G peptide and the c-Crk SH3-N domain. The C3G peptide is represented by the left-handed shaded ribbon, and peptide residues that interact with the SH3 domain are indicated by shaded circles. Residues in c-Crk SH3-N that interact with the peptide are indicated by oval boxes (for hydrophobic residues) and rectangular boxes (for acidic residues). Distances (in å) between interacting residues are shown for the nearest pair of carbon atoms (for hydrophobic interactions) and between donor atom and acceptor atom for hydrogen bonds. Figure 3. Schematic diagram showing interactions between the C3G peptide and the c-Crk SH3-N domain. The C3G peptide is represented by the left-handed shaded ribbon, and peptide residues that interact with the SH3 domain are indicated by shaded circles. Residues in c-Crk SH3-N that interact with the peptide are indicated by oval boxes (for hydrophobic residues) and rectangular boxes (for acidic residues). Distances (in å) between interacting residues are shown for the nearest pair of carbon atoms (for hydrophobic interactions) and between donor atom and acceptor atom for hydrogen bonds.		Figure 5. Figure 5. Schematic diagram of the stereochemistry of the lysine–carboxylate interaction at position P[−3] (after lppolito et al. [26]). The amino group of the peptide lysine is shown in a Newman projection, and the relative disposition of the carboxylate groups and the hydrogen-bonding hydrogens in the C3G/Crk complex are shown. Figure 5. Schematic diagram of the stereochemistry of the lysine–carboxylate interaction at position P[−3] (after lppolito et al. [[3]26]). The amino group of the peptide lysine is shown in a Newman projection, and the relative disposition of the carboxylate groups and the hydrogen-bonding hydrogens in the C3G/Crk complex are shown.

PROCHECK

	Headers