Protein tyrosine phosphatase SHP-1 specifically recognizes C-terminal residues of its substrates via helix alpha0.
The catalytic domain of protein tyrosine phosphatase SHP-1 possesses distinct substrate specificity. It recognizes the P-3 to P-5 residues of its substrates via the beta5-loop-beta6 region. To study the substrate specificity further, we determined the structure of the catalytic domain of SHP-1 (C455S) complexed with a less-favorable-substrate peptide originated from SIRPalpha. The complex has disordered N-terminal peptide structure and reduced interactions between the N-terminal peptide and the beta5-loop-beta6 region. This could be the basis for the lower affinity of peptide pY(427) for the catalytic domain of SHP-1. In addition, by comparing the SHP-1/less-favorable peptide complex structure with the SHP-1/substrate complex structures, we identified a novel substrate-recognition site in the catalytic domain of SHP-1. This site was formed by helix alpha0 and the alpha5-loop-alpha6 motif of SHP-1, and specifically bound residues at the P + 4 and further C-terminal positions of peptide substrates.
Yang
J
J
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Cheng
Z
Z
Niu
T
T
Liang
X
X
Zhao
Z J
ZJ
Zhou
G W
GW
D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D055672:Static Electricity; D013379:Substrate Specificity
D047908:Intracellular Signaling Peptides and Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases