4cmz | pdb_00004cmz
An intertwined homodimer of the PDZ homology domain of periaxin
Structural highlights
Disease[PRAX_HUMAN] Dejerine-Sottas syndrome;Charcot-Marie-Tooth disease type 4F. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function[PRAX_HUMAN] Seems to be required for maintenance of peripheral nerve myelin sheath. May have a role in axon-glial interactions, possibly by interacting with the cytoplasmic domains of integral membrane proteins such as myelin-associated glycoprotein in the periaxonal regions of the Schwann cell plasma membrane. May have a role in the early phases of myelin deposition. Publication Abstract from PubMedPeriaxin (PRX) is an abundant protein in the peripheral nervous system, with an important role in myelination. PRX participates in large molecular complexes, most likely through the interactions of its N-terminal PSD-95/Discs-large/ZO-1 (PDZ)-like domain. We present the crystal structures of the PDZ-like domains from PRX and its homologue AHNAK nucleoprotein 2 (AHNAK2). The unique intertwined, domain-swapped dimers provide a structural basis for the homodimerization of both proteins. The core of the homodimer is formed by a 6-stranded antiparallel beta sheet, with every other strand from a different chain. The AHNAK2 PDZ domain structure contains a bound class III ligand peptide. The binding pocket is preformed, and the peptide-PDZ interactions have unique aspects, including two salt bridges and weak recognition of the peptide C terminus. Tight homodimerization may be central to the scaffolding functions of PRX and AHNAK2 in molecular complexes linking the extracellular matrix to the cytoskeletal network. Periaxin and AHNAK nucleoprotein 2 form intertwined homodimers through domain swapping.,Han H, Kursula P J Biol Chem. 2014 Mar 27. PMID:24675079[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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