3ajb | pdb_00003ajb
Crystal Structure of human Pex3p in complex with N-terminal Pex19p peptide
Structural highlights
DiseasePEX3_HUMAN Defects in PEX3 are the cause of peroxisome biogenesis disorder complementation group 12 (PBD-CG12) [MIM:614882; also known as PBD-CGG. PBD refers to a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. The PBD group is comprised of four disorders: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum. The PBD group is genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies.[1] Defects in PEX3 are a cause of peroxisome biogenesis disorder 10A (PBD10A) [MIM:614882. A fatal peroxisome biogenesis disorder characterized by dysmorphic facial features, hepatomegaly, ocular abnormalities, renal cysts, hearing impairment, profound psychomotor retardation, severe hypotonia and neonatal seizures. Death occurs within the first year of life.[2] [3] FunctionPEX3_HUMAN Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes.[4] [5] Publication Abstract from PubMedPeroxisomes require peroxin (Pex) proteins for their biogenesis. The interaction between Pex3p, which resides on the peroxisomal membrane, and Pex19p, which resides in the cytosol, is crucial for peroxisome formation and the post-translational targeting of peroxisomal membrane proteins (PMPs). It is not known how Pex3p promotes the specific interaction with Pex19p for the purpose of PMP translocation. Here, we present the three-dimensional structure of the complex between a cytosolic domain of Pex3p and the binding-region peptide of Pex19p. The overall shape of Pex3p is a prolate spheroid with a novel fold, the 'twisted six-helix bundle.' The Pex19p-binding site is at an apex of the Pex3p spheroid. A 16-residue region of the Pex19p peptide forms an alpha-helix and makes a contact with Pex3p; this helix is disordered in the unbound state. The Pex19p peptide contains a characteristic motif, consisting of the leucine triad (Leu18, Leu21, Leu22), and Phe29, which are critical for the Pex3p binding and peroxisome biogenesis. Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p.,Sato Y, Shibata H, Nakatsu T, Nakano H, Kashiwayama Y, Imanaka T, Kato H EMBO J. 2010 Dec 15;29(24):4083-93. Epub 2010 Nov 19. PMID:21102411[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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