| Structural highlights
Disease
[SPG7_HUMAN] Defects in SPG7 are the cause of spastic paraplegia autosomal recessive type 7 (SPG7) [MIM:607259]. Spastic paraplegia is a degenerative spinal cord disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. SPG7 is a complex form. Additional clinical features are cerebellar syndrome, supranuclear palsy, and cognitive impairment, particularly disturbance of attention and executive functions.[1] [2] [3] [4] Note=Defects in SPG7 may cause autosomal recessive osteogenesis imperfecta (OI). Osteogenesis imperfecta defines a group of connective tissue disorders characterized by bone fragility and low bone mass. Clinical features of SPG7-related osteogenesis imperfecta include recurrent fractures, mild bone deformities, delayed tooth eruption, normal hearing and white sclera.
Function
[SPG7_HUMAN] Putative ATP-dependent zinc metalloprotease.
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 PubMed
Paraplegin is an m-AAA protease of the mitochondrial inner membrane that is linked to hereditary spastic paraplegias. The gene encodes an FtsH-homology protease domain in tandem with an AAA+ homology ATPase domain. The protein is believed to form a hexamer that uses ATPase-driven conformational changes in its AAA-domain to deliver substrate peptides to its protease domain. We present the crystal structure of the AAA-domain of human paraplegin bound to ADP at 2.2 A. This enables assignment of the roles of specific side chains within the catalytic cycle, and provides the structural basis for understanding the mechanism of disease mutations. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.
Crystal structure of the ATPase domain of the human AAA+ protein paraplegin/SPG7.,Karlberg T, van den Berg S, Hammarstrom M, Sagemark J, Johansson I, Holmberg-Schiavone L, Schuler H PLoS One. 2009 Oct 20;4(10):e6975. PMID:19841671[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Casari G, De Fusco M, Ciarmatori S, Zeviani M, Mora M, Fernandez P, De Michele G, Filla A, Cocozza S, Marconi R, Durr A, Fontaine B, Ballabio A. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell. 1998 Jun 12;93(6):973-83. PMID:9635427
- ↑ Elleuch N, Depienne C, Benomar A, Hernandez AM, Ferrer X, Fontaine B, Grid D, Tallaksen CM, Zemmouri R, Stevanin G, Durr A, Brice A. Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia. Neurology. 2006 Mar 14;66(5):654-9. PMID:16534102 doi:10.1212/01.wnl.0000201185.91110.15
- ↑ Warnecke T, Duning T, Schwan A, Lohmann H, Epplen JT, Young P. A novel form of autosomal recessive hereditary spastic paraplegia caused by a new SPG7 mutation. Neurology. 2007 Jul 24;69(4):368-75. PMID:17646629 doi:69/4/368
- ↑ Bonn F, Pantakani K, Shoukier M, Langer T, Mannan AU. Functional evaluation of paraplegin mutations by a yeast complementation assay. Hum Mutat. 2010 May;31(5):617-21. doi: 10.1002/humu.21226. PMID:20186691 doi:10.1002/humu.21226
- ↑ Karlberg T, van den Berg S, Hammarstrom M, Sagemark J, Johansson I, Holmberg-Schiavone L, Schuler H. Crystal structure of the ATPase domain of the human AAA+ protein paraplegin/SPG7. PLoS One. 2009 Oct 20;4(10):e6975. PMID:19841671 doi:10.1371/journal.pone.0006975
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