TY - JOUR
T1 - A novel, specific interaction involving the Csk SH3 domain and its natural ligand
AU - Ghose, Ranajeet
AU - Shekhtman, Alexander
AU - Goger, Michael J.
AU - Ji, Hong
AU - Cowburn, David
N1 - Funding Information:
R.G. would like to thank D. Fushman for useful discussions and for providing the DYNAMICS package and P. Loria for providing the relaxation compensated CPMG pulse sequence. The authors thank P.A. Cole for useful discussions. This work has been supported by a grant from the National Institutes of Health and a fellowship from the National Cancer Institute to A.S.
PY - 2001
Y1 - 2001
N2 - C-terminal Src kinase (Csk) takes part in a highly specific, high affinity interaction via its Src homology 3 (SH3) domain with the proline-enriched tyrosine phosphatase PEP in hematopoietic cells. The solution structure of the Csk-SH3 domain in complex with a 25-residue peptide from the Pro/Glu/Ser/Thr-rich (PEST) domain of PEP reveals the basis for this specific peptide recognition motif involving an SH3 domain. Three residues, Ala 40, Thr 42 and Lys 43, in the SH3 domain of Csk specifically recognize two hydrophobic residues, Ile 625 and Val 626, in the proline-rich sequence of the PEST domain of PER These two residues are C-terminal to the conventional prolinerich SH3 domain recognition sequence of PEP. This interaction is required in addition to the classic polyproline helix (PPII) recognition by the Csk-SH3 domain for the association between Csk and PEP in vivo. NMR relaxation analysis suggests that Csk-SH3 has different dynamic properties in the various subsites important for peptide recognition.
AB - C-terminal Src kinase (Csk) takes part in a highly specific, high affinity interaction via its Src homology 3 (SH3) domain with the proline-enriched tyrosine phosphatase PEP in hematopoietic cells. The solution structure of the Csk-SH3 domain in complex with a 25-residue peptide from the Pro/Glu/Ser/Thr-rich (PEST) domain of PEP reveals the basis for this specific peptide recognition motif involving an SH3 domain. Three residues, Ala 40, Thr 42 and Lys 43, in the SH3 domain of Csk specifically recognize two hydrophobic residues, Ile 625 and Val 626, in the proline-rich sequence of the PEST domain of PER These two residues are C-terminal to the conventional prolinerich SH3 domain recognition sequence of PEP. This interaction is required in addition to the classic polyproline helix (PPII) recognition by the Csk-SH3 domain for the association between Csk and PEP in vivo. NMR relaxation analysis suggests that Csk-SH3 has different dynamic properties in the various subsites important for peptide recognition.
UR - http://www.scopus.com/inward/record.url?scp=0034753803&partnerID=8YFLogxK
U2 - 10.1038/nsb1101-998
DO - 10.1038/nsb1101-998
M3 - Article
C2 - 11685249
AN - SCOPUS:0034753803
SN - 1072-8368
VL - 8
SP - 998
EP - 1004
JO - Nature Structural Biology
JF - Nature Structural Biology
IS - 11
ER -