PDBsum entry 5tqs

Hydrolase

PDB id: 5tqs

Contents

Protein chains

101 a.a.

Ligands

LEU-TYR-PTR-TRP-ASP-GLN

ASN-LEU-TYR-PTR-TRP-ASP-GLN

ASP-ASN-LEU-TYR-PTR-TRP-ASP

ASP-ASN-LEU-TYR-PTR-TRP-ASP-GLN

Waters ×268

PDB id:

5tqs

Name:

Hydrolase

Title:

PhospholipasE C gamma-1 c-terminal sh2 domain bound to a phosphopeptide derived from the receptor tyrosine kinase erbb2

Structure:

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1. Chain: a, b, c, d. Fragment: unp residues 663-759. Synonym: plc-148,phosphoinositide phospholipasE C-gamma-1, phospholipasE C-ii,plc-ii,phospholipasE C-gamma-1,plc-gamma-1. Engineered: yes. Receptor protein-tyrosine kinase. Chain: e, f, h, g.

Source:

Bos taurus. Bovine. Organism_taxid: 9913. Gene: plcg1. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_cell_line: bl21(de3). Synthetic: yes. Homo sapiens.

Resolution:

1.88Å R-factor: 0.191 R-free: 0.237

Authors:

D.S.Wuttke,M.A.Mckercher

Key ref:

M.A.McKercher et al. (2017). Multimodal Recognition of Diverse Peptides by the C-Terminal SH2 Domain of Phospholipase C-γ1 Protein. Biochemistry, 56, 2225-2237. PubMed id: 28376302 DOI: 10.1021/acs.biochem.7b00023

Date:

24-Oct-16 Release date: 19-Apr-17

Protein chains

P08487  (PLCG1_BOVIN) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 from Bos taurus

Seq: 1291 a.a.

Struc: 101 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.4.11 - phosphoinositide phospholipase C.
• Pathway: myo-Inositol Phosphate Metabolism
• Reaction: a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-diacyl-sn-glycerol + H⁺

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

Added reference

DOI no: 10.1021/acs.biochem.7b00023

Biochemistry 56:2225-2237 (2017)

PubMed id: 28376302

Multimodal Recognition of Diverse Peptides by the C-Terminal SH2 Domain of Phospholipase C-γ1 Protein.

M.A.McKercher, X.Guan, Z.Tan, D.S.Wuttke.

ABSTRACT

SH2 domains recognize phosphotyrosine (pY)-containing peptide ligands and play key roles in the regulation of receptor tyrosine kinase pathways. Each SH2 domain has individualized specificity, encoded in the amino acids neighboring the pY, for defined targets that convey their distinct functions. The C-terminal SH2 domain (PLCC) of the phospholipase C-γ1 full-length protein (PLCγ1) typically binds peptides containing small and hydrophobic amino acids adjacent to the pY, including a peptide derived from platelet-derived growth factor receptor B (PDGFRB) and an intraprotein recognition site (Y783 of PLCγ1) involved in the regulation of the protein's lipase activity. Remarkably, PLCC also recognizes unexpected peptides containing amino acids with polar or bulky side chains that deviate from this pattern. This versatility in recognition specificity may allow PLCγ1 to participate in diverse, previously unrecognized, signaling pathways in response to binding chemically dissimilar partners. We have used structural approaches, including nuclear magnetic resonance and X-ray crystallography, to elucidate the mechanisms of noncognate peptide binding to PLCC by ligands derived from receptor tyrosine kinase ErbB2 and from the insulin receptor. The high-resolution peptide-bound structures reveal that PLCC has a relatively static backbone but contains a chemically rich protein surface comprised of a combination of hydrophobic pockets and amino acids with charged side chains. We demonstrate that this expansive and chemically diverse PLCC interface, in addition to peptide conformational plasticity, permits PLCC to recognize specific noncognate peptide ligands with multimodal specificity.