2c0l | pdb_00002c0l
TPR DOMAIN OF HUMAN PEX5P IN COMPLEX WITH HUMAN MSCP2
Structural highlights
Disease[PEX5_HUMAN] Defects in PEX5 are the cause of peroxisome biogenesis disorder 2A (PBD2A) [MIM:214110]. A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and characterized clinically by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life.[1] Defects in PEX5 are the cause of peroxisome biogenesis disorder 2B (PBD2B) [MIM:202370]. A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. [NLTP_HUMAN] Defects in SCP2 are a cause of leukoencephalopathy with dystonia and motor neuropathy (LDMN) [MIM:613724]; also known as sterol carrier protein 2 deficiency. LDMN is a syndrome characterized by leukoencephalopathy, dystonic head tremor, spasmodic torticollis and reduced tendon reflexes in lower extremities. Additional features include hyposmia, pathologic saccadic eye movements, a slight hypoacusis, accumulation of branched-chain pristanic acid in plasma, and the presence of abnormal bile alcohol glucuronides in urine.[2] Function[PEX5_HUMAN] Binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import.[3] [4] [5] [NLTP_HUMAN] Mediates in vitro the transfer of all common phospholipids, cholesterol and gangliosides between membranes. May play a role in regulating steroidogenesis.[6] [7] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPeroxisomes require the translocation of folded and functional target proteins of various sizes across the peroxisomal membrane. We have investigated the structure and function of the principal import receptor Pex5p, which recognizes targets bearing a C-terminal peroxisomal targeting signal type 1. Crystal structures of the receptor in the presence and absence of a peroxisomal target, sterol carrier protein 2, reveal major structural changes from an open, snail-like conformation into a closed, circular conformation. These changes are caused by a long loop C terminal to the 7-fold tetratricopeptide repeat segments. Mutations in residues of this loop lead to defects in peroxisomal import in human fibroblasts. The structure of the receptor/cargo complex demonstrates that the primary receptor-binding site of the cargo is structurally and topologically autonomous, enabling the cargo to retain its native structure and function. Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p.,Stanley WA, Filipp FV, Kursula P, Schuller N, Erdmann R, Schliebs W, Sattler M, Wilmanns M Mol Cell. 2006 Dec 8;24(5):653-63. PMID:17157249[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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