5tq1

From Proteopedia

Phospholipase C gamma-1 C-terminal SH2 domain bound to a phosphopeptide derived from the insulin receptor

PDB ID 5tq1

Drag the structure with the mouse to rotate

Structural highlights

5tq1 is a 2 chain structure with sequence from Bos taurus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.485Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PLCG1_BOVIN Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration (By similarity).

Publication Abstract from PubMed

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-gamma1 full-length protein (PLCgamma1) 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 PLCgamma1) 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 PLCgamma1 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.

Multimodal Recognition of Diverse Peptides by the C-Terminal SH2 Domain of Phospholipase C-gamma1 Protein.,McKercher MA, Guan X, Tan Z, Wuttke DS Biochemistry. 2017 Apr 11. doi: 10.1021/acs.biochem.7b00023. PMID:28376302^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ McKercher MA, Guan X, Tan Z, Wuttke DS. Multimodal Recognition of Diverse Peptides by the C-Terminal SH2 Domain of Phospholipase C-gamma1 Protein. Biochemistry. 2017 Apr 11. doi: 10.1021/acs.biochem.7b00023. PMID:28376302 doi:http://dx.doi.org/10.1021/acs.biochem.7b00023