High Definition Solution Structure of PED/PEA-15 Death Effector DomainHigh Definition Solution Structure of PED/PEA-15 Death Effector Domain

Structural highlights

2ls7 is a 1 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PEA15_MOUSE Blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade. Inhibits RPS6KA3 activities by retaining it in the cytoplasm. Inhibits both TNFRSF6- and TNFRSF1A-mediated CASP8 activity and apoptosis. Regulates glucose transport by controlling both the content of SLC2A1 glucose transporters on the plasma membrane and the insulin-dependent trafficking of SLC2A4 from the cell interior to the surface (By similarity).

Publication Abstract from PubMed

Death effector domain (DED) proteins constitute a subfamily of the large death domain superfamily that is primarily involved in apoptosis pathways. DED structures have characteristic side chain-side chain interactions among polar residues on the protein surface, forming a network of hydrogen bonds and salt bridges. The polar interaction network is functionally important in promoting protein-protein interactions by maintaining optimal side chain orientations. We have refined the solution DED structure of the PED/PEA-15 protein, a representative member of DED subfamily, using traditional NMR restraints with the addition of residual dipolar coupling (RDC) restraints from two independent alignment media, and employed the explicit solvent refinement protocol. The newly refined DED structure of PED/PEA-15 possesses higher structural quality as indicated by WHAT IF Z-scores, with most significant improvement in the backbone conformation normality quality factor. This higher quality DED structure of PED/PEA-15 leads to the identification of a number of key polar side chain interactions, which are not typically observed in NMR protein structures. The elucidation of polar side chain interactions is a key step towards the understanding of protein-protein interactions involving the death domain superfamily. The NMR structures with extensive details of protein structural features are thereby termed high-definition (HD) NMR structures.

High-definition NMR structure of PED/PEA-15 death effector domain reveals details of key polar side chain interactions.,Twomey EC, Wei Y Biochem Biophys Res Commun. 2012 Jul 20;424(1):141-6. Epub 2012 Jun 23. PMID:22732408[1]

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

References

  1. Twomey EC, Wei Y. High-definition NMR structure of PED/PEA-15 death effector domain reveals details of key polar side chain interactions. Biochem Biophys Res Commun. 2012 Jul 20;424(1):141-6. Epub 2012 Jun 23. PMID:22732408 doi:10.1016/j.bbrc.2012.06.091
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