View source for 6b9e


==Human ATL1 mutant - R77A / F151S bound to GDP==
<StructureSection load='6b9e' size='340' side='right' caption='[[6b9e]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6b9e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B9E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B9E FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATL1, GBP3, SPG3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6b9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b9e OCA], [http://pdbe.org/6b9e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b9e RCSB], [http://www.ebi.ac.uk/pdbsum/6b9e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b9e ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/ATLA1_HUMAN ATLA1_HUMAN]] Hereditary sensory and autonomic neuropathy type 1;Autosomal dominant spastic paraplegia type 3. Spastic paraplegia autosomal dominant 3 (SPG3) [MIM:[http://omim.org/entry/182600 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.<ref>PMID:17321752</ref> <ref>PMID:11685207</ref> <ref>PMID:12112092</ref> <ref>PMID:12939451</ref> <ref>PMID:14695538</ref> <ref>PMID:15184642</ref> <ref>PMID:16533974</ref> <ref>PMID:17427918</ref> <ref>PMID:20932283</ref> <ref>PMID:20718791</ref>   Hereditary sensory neuropathy 1D (HSN1D) [MIM:[http://omim.org/entry/613708 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.<ref>PMID:21194679</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/ATLA1_HUMAN 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.<ref>PMID:14506257</ref> <ref>PMID:17321752</ref> <ref>PMID:18270207</ref> <ref>PMID:19665976</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The dynamin-related GTPase atlastin (ATL) catalyzes membrane fusion of the endoplasmic reticulum (ER) and thus establishes a network of branched membrane tubules. When ATL function is compromised, the morphology of the ER deteriorates, and these defects can result in neurological disorders such as hereditary spastic paraplegia (HSP) and hereditary sensory neuropathy (HSN). ATLs harness the energy of GTP hydrolysis to initiate a series of conformational changes that enable homodimerization and subsequent membrane fusion. Disease-associated amino acid substitutions cluster in regions adjacent to ATL's catalytic site, but the consequences for the GTPase's molecular mechanism are often poorly understood. Here, we elucidate structural and functional defects of an atypical HSP mutant, ATL1-F(151)S that is impaired in its nucleotide-hydrolysis cycle, but can still adopt a high-affinity homodimer when bound to a transition-state analog. Crystal structures of mutant proteins yielded models of the monomeric pre- and post-hydrolysis states of ATL. Together, these findings define a mechanism for allosteric coupling in which F(151) is the central residue in a hydrophobic interaction network connecting the active site to an inter-domain interface responsible for nucleotide loading.

A hereditary spastic paraplegia-associated atlastin variant exhibits defective allosteric coupling in the catalytic core.,O'Donnell JP, Byrnes LJ, Cooley RB, Sondermann H J Biol Chem. 2017 Nov 27. pii: RA117.000380. doi: 10.1074/jbc.RA117.000380. PMID:29180453<ref>PMID:29180453</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6b9e" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Donnell, J P.O]]
[[Category: Sondermann, H]]
[[Category: Dynamin related protein]]
[[Category: Gtpase]]
[[Category: Hydrolase]]
[[Category: Hydrolysis-deficient]]