4q2p

From Proteopedia

NHERF3 PDZ2 in Complex with a Phage-Derived Peptide

PDB ID 4q2p

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Structural highlights

4q2p is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NHRF3_HUMAN A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with SLC9A3R1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity. May function to connect SCARB1 with the cellular machineries for intracellular cholesterol transport and/or metabolism. May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function (By similarity).

Publication Abstract from PubMed

PDZ (PSD-95/Discs-large/ZO1) domains are interaction modules that typically bind to specific C-terminal sequences of partner proteins and assemble signaling complexes in multicellular organisms. We have analyzed the existing database of PDZ domain structures in the context of a specificity tree based on binding specificities defined by peptide-phage binding selections. We have identified 16 structures of PDZ domains in complex with high-affinity ligands and have elucidated four additional structures to assemble a structural database that covers most of the branches of the PDZ specificity tree. A detailed comparison of the structures reveals features that are responsible for the diverse specificities across the PDZ domain family. Specificity differences can be explained by differences in PDZ residues that are in contact with the peptide ligands, but these contacts involve both side-chain and main-chain interactions. Most PDZ domains bind peptides in a canonical conformation in which the ligand main chain adopts an extended beta-strand conformation by interacting in an antiparallel fashion with a PDZ beta-strand. However, a subset of PDZ domains bind peptides with a bent main-chain conformation and the specificities of these non-canonical domains could not be explained based on canonical structures. Our analysis provides a structural portrait of the PDZ domain family, which serves as a guide in understanding the structural basis for the diverse specificities across the family.

A Structural Portrait of the PDZ Domain Family.,Ernst A, Appleton BA, Ivarsson Y, Zhang Y, Gfeller D, Wiesmann C, Sidhu SS J Mol Biol. 2014 Aug 23. pii: S0022-2836(14)00431-8. doi:, 10.1016/j.jmb.2014.08.012. PMID:25158098^[1]

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

References

↑ Ernst A, Appleton BA, Ivarsson Y, Zhang Y, Gfeller D, Wiesmann C, Sidhu SS. A Structural Portrait of the PDZ Domain Family. J Mol Biol. 2014 Aug 23. pii: S0022-2836(14)00431-8. doi:, 10.1016/j.jmb.2014.08.012. PMID:25158098 doi:http://dx.doi.org/10.1016/j.jmb.2014.08.012