3qof

From Proteopedia
Jump to navigation Jump to search

Crystal structure of the cytosolic domain of human atlastin-1 in complex with GDP, orthorhombic formCrystal structure of the cytosolic domain of human atlastin-1 in complex with GDP, orthorhombic form

Structural highlights

3qof is a 4 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 2.802Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ATLA1_HUMAN Hereditary sensory and autonomic neuropathy type 1;Autosomal dominant spastic paraplegia type 3. Spastic paraplegia autosomal dominant 3 (SPG3) [MIM:182600: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Note=The disease is caused by mutations affecting the gene represented in this entry.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] Hereditary sensory neuropathy 1D (HSN1D) [MIM:613708: A disease characterized by adult-onset distal axonal sensory neuropathy leading to mutilating ulcerations as well as hyporeflexia. Some patients may show features suggesting upper neuron involvement. Note=The disease is caused by mutations affecting the gene represented in this entry.[11]

Function

ATLA1_HUMAN GTPase tethering membranes through formation of trans-homooligomer and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis. May also regulate Golgi biogenesis. May regulate axonal development.[12] [13] [14] [15]

Publication Abstract from PubMed

The generation of the tubular network of the endoplasmic reticulum (ER) requires homotypic membrane fusion that is mediated by the dynamin-like, membrane-bound GTPase atlastin (ATL). Here, we have determined crystal structures of the cytosolic segment of human ATL1, which give insight into the mechanism of membrane fusion. The structures reveal a GTPase domain and athree-helix bundle, connected by a linker region. One structure corresponds to a prefusion state, in which ATL molecules in apposing membranes interact through their GTPase domains to form a dimer with the nucleotides bound at the interface. The other structure corresponds to a postfusion state generated after GTP hydrolysis and phosphate release. Compared with the prefusion structure, the three-helix bundles of the two ATL molecules undergo a major conformational change relative to the GTPase domains, which could pull the membranes together. The proposed fusion mechanism is supported by biochemical experiments and fusion assays with wild-type and mutant full-length Drosophila ATL. These experiments also show that membrane fusion is facilitated by the C-terminal cytosolic tails following the two transmembrane segments. Finally, our results show that mutations in ATL1 causing hereditary spastic paraplegia compromise homotypic ER fusion.

Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes.,Bian X, Klemm RW, Liu TY, Zhang M, Sun S, Sui X, Liu X, Rapoport TA, Hu J Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):3976-81. Epub 2011 Feb 22. PMID:21368113[16]

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

See Also

References

  1. ↑ Namekawa M, Muriel MP, Janer A, Latouche M, Dauphin A, Debeir T, Martin E, Duyckaerts C, Prigent A, Depienne C, Sittler A, Brice A, Ruberg M. Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER/Golgi interface and Golgi morphogenesis. Mol Cell Neurosci. 2007 May;35(1):1-13. Epub 2007 Jan 26. PMID:17321752 doi:10.1016/j.mcn.2007.01.012
  2. ↑ Zhao X, Alvarado D, Rainier S, Lemons R, Hedera P, Weber CH, Tukel T, Apak M, Heiman-Patterson T, Ming L, Bui M, Fink JK. Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nat Genet. 2001 Nov;29(3):326-31. PMID:11685207 doi:10.1038/ng758
  3. ↑ Muglia M, Magariello A, Nicoletti G, Patitucci A, Gabriele AL, Conforti FL, Mazzei R, Caracciolo M, Ardito B, Lastilla M, Tedeschi G, Quattrone A. Further evidence that SPG3A gene mutations cause autosomal dominant hereditary spastic paraplegia. Ann Neurol. 2002 Jun;51(6):794-5. PMID:12112092 doi:10.1002/ana.10185
  4. ↑ Dalpozzo F, Rossetto MG, Boaretto F, Sartori E, Mostacciuolo ML, Daga A, Bassi MT, Martinuzzi A. Infancy onset hereditary spastic paraplegia associated with a novel atlastin mutation. Neurology. 2003 Aug 26;61(4):580-1. PMID:12939451
  5. ↑ Sauter SM, Engel W, Neumann LM, Kunze J, Neesen J. Novel mutations in the Atlastin gene (SPG3A) in families with autosomal dominant hereditary spastic paraplegia and evidence for late onset forms of HSP linked to the SPG3A locus. Hum Mutat. 2004 Jan;23(1):98. PMID:14695538 doi:10.1002/humu.9205
  6. ↑ D'Amico A, Tessa A, Sabino A, Bertini E, Santorelli FM, Servidei S. Incomplete penetrance in an SPG3A-linked family with a new mutation in the atlastin gene. Neurology. 2004 Jun 8;62(11):2138-9. PMID:15184642
  7. ↑ Rainier S, Sher C, Reish O, Thomas D, Fink JK. De novo occurrence of novel SPG3A/atlastin mutation presenting as cerebral palsy. Arch Neurol. 2006 Mar;63(3):445-7. PMID:16533974 doi:10.1001/archneur.63.3.445
  8. ↑ Meijer IA, Dion P, Laurent S, Dupre N, Brais B, Levert A, Puymirat J, Rioux MF, Sylvain M, Zhu PP, Soderblom C, Stadler J, Blackstone C, Rouleau GA. Characterization of a novel SPG3A deletion in a French-Canadian family. Ann Neurol. 2007 Jun;61(6):599-603. PMID:17427918 doi:10.1002/ana.21114
  9. ↑ Alvarez V, Sanchez-Ferrero E, Beetz C, Diaz M, Alonso B, Corao AI, Gamez J, Esteban J, Gonzalo JF, Pascual-Pascual SI, Lopez de Munain A, Moris G, Ribacoba R, Marquez C, Rosell J, Marin R, Garcia-Barcina MJ, Del Castillo E, Benito C, Coto E. Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia. BMC Neurol. 2010 Oct 8;10:89. doi: 10.1186/1471-2377-10-89. PMID:20932283 doi:10.1186/1471-2377-10-89
  10. ↑ McCorquodale DS 3rd, Ozomaro U, Huang J, Montenegro G, Kushman A, Citrigno L, Price J, Speziani F, Pericak-Vance MA, Zuchner S. Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia. Clin Genet. 2011 Jun;79(6):523-30. doi: 10.1111/j.1399-0004.2010.01501.x. PMID:20718791 doi:10.1111/j.1399-0004.2010.01501.x
  11. ↑ Guelly C, Zhu PP, Leonardis L, Papic L, Zidar J, Schabhuttl M, Strohmaier H, Weis J, Strom TM, Baets J, Willems J, De Jonghe P, Reilly MM, Frohlich E, Hatz M, Trajanoski S, Pieber TR, Janecke AR, Blackstone C, Auer-Grumbach M. Targeted high-throughput sequencing identifies mutations in atlastin-1 as a cause of hereditary sensory neuropathy type I. Am J Hum Genet. 2011 Jan 7;88(1):99-105. doi: 10.1016/j.ajhg.2010.12.003. Epub, 2010 Dec 30. PMID:21194679 doi:10.1016/j.ajhg.2010.12.003
  12. ↑ Zhu PP, Patterson A, Lavoie B, Stadler J, Shoeb M, Patel R, Blackstone C. Cellular localization, oligomerization, and membrane association of the hereditary spastic paraplegia 3A (SPG3A) protein atlastin. J Biol Chem. 2003 Dec 5;278(49):49063-71. Epub 2003 Sep 23. PMID:14506257 doi:10.1074/jbc.M306702200
  13. ↑ Namekawa M, Muriel MP, Janer A, Latouche M, Dauphin A, Debeir T, Martin E, Duyckaerts C, Prigent A, Depienne C, Sittler A, Brice A, Ruberg M. Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER/Golgi interface and Golgi morphogenesis. Mol Cell Neurosci. 2007 May;35(1):1-13. Epub 2007 Jan 26. PMID:17321752 doi:10.1016/j.mcn.2007.01.012
  14. ↑ Rismanchi N, Soderblom C, Stadler J, Zhu PP, Blackstone C. Atlastin GTPases are required for Golgi apparatus and ER morphogenesis. Hum Mol Genet. 2008 Jun 1;17(11):1591-604. doi: 10.1093/hmg/ddn046. Epub 2008 Feb, 12. PMID:18270207 doi:10.1093/hmg/ddn046
  15. ↑ Hu J, Shibata Y, Zhu PP, Voss C, Rismanchi N, Prinz WA, Rapoport TA, Blackstone C. A class of dynamin-like GTPases involved in the generation of the tubular ER network. Cell. 2009 Aug 7;138(3):549-61. PMID:19665976 doi:S0092-8674(09)00628-X
  16. ↑ Bian X, Klemm RW, Liu TY, Zhang M, Sun S, Sui X, Liu X, Rapoport TA, Hu J. Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes. Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):3976-81. Epub 2011 Feb 22. PMID:21368113 doi:10.1073/pnas.1101643108

3qof, resolution 2.80Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=3qof&oldid=3936519"