3l9b

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[[Image:3l9b.jpg|left|200px]]
 
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==Crystal Structure of Rat Otoferlin C2A==
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The line below this paragraph, containing "STRUCTURE_3l9b", creates the "Structure Box" on the page.
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<StructureSection load='3l9b' size='340' side='right'caption='[[3l9b]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3l9b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L9B FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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{{STRUCTURE_3l9b| PDB=3l9b | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3l9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l9b OCA], [https://pdbe.org/3l9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l9b RCSB], [https://www.ebi.ac.uk/pdbsum/3l9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l9b ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/OTOF_RAT OTOF_RAT] Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion and in the control of neurotransmitter release at these output synapses. Interacts in a calcium-dependent manner to the presynaptic SNARE proteins at ribbon synapses of cochlear inner hair cells (IHCs) to trigger exocytosis of neurotransmitter. Also essential to synaptic exocytosis in immature outer hair cells (OHCs). May also play a role within the recycling of endosomes (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Otoferlin (Otof), whose genetic mutations cause profound deafness in humans, is a protein composed of at least six C(2) domains, which are known as Ca(2)(+)-binding and phospholipid-binding regions. Mammalian ferlin proteins are proposed to act in membrane fusion events, with Otof being specifically required for exocytosis in auditory hair cells. Ferlin C(2) domains exhibit a rather low level of sequence similarity to those of synaptotagmins, protein kinase C isoforms, or phospholipases. Here, we report the crystal structure of the N-terminal C(2) domain of Otof (C(2)A) at 1.95-A resolution. In contrast to previous predictions, we found that this C(2) domain is complete with eight beta-strands. Comparing the structure of Otof C(2)A to those of other C(2) domains revealed one top loop in Otof to be significantly shorter. This results in a depression of the surface, which is positively charged for the Otof C(2)A domain, and contrasts with the head-like protrusion surrounded by a negatively charged "neck" typically found in other C(2) domains. Isothermal titration calorimetry and circular dichroism spectroscopy studies confirmed that Otof C(2)A is unable to bind Ca(2+), while the synaptotagmin-1 C(2)A domain exhibited Ca(2+) binding under the same conditions. Furthermore, floatation assays revealed a failure of Otof C(2)A to bind to phospholipid membranes. Accordingly, no positively charged beta-groove-like surface structure, which is known to bind phosphatidylinositol-4,5-bisphosphate in other C(2) domains, was found at the respective position in Otof C(2)A. Taken together, these data demonstrate that the Otof C(2)A domain differs structurally and functionally from other C(2) domains.
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===Crystal Structure of Rat Otoferlin C2A===
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The crystal structure of the C(2)A domain of otoferlin reveals an unconventional top loop region.,Helfmann S, Neumann P, Tittmann K, Moser T, Ficner R, Reisinger E J Mol Biol. 2011 Feb 25;406(3):479-90. doi: 10.1016/j.jmb.2010.12.031. Epub 2011 , Jan 7. PMID:21216247<ref>PMID:21216247</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==About this Structure==
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</div>
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[[3l9b]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L9B OCA].
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<div class="pdbe-citations 3l9b" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Helfmann, S.]]
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[[Category: Helfmann S]]
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[[Category: Neumann, P.]]
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[[Category: Neumann P]]

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Crystal Structure of Rat Otoferlin C2A

PDB ID 3l9b

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