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3l9b

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Revision as of 07:31, 23 December 2016

Crystal Structure of Rat Otoferlin C2A

Structural highlights

3l9b is a 1 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Fer1l2, Otof (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).

Publication Abstract from PubMed

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.

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^[1]

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

References

↑ Helfmann S, Neumann P, Tittmann K, Moser T, Ficner R, Reisinger E. The crystal structure of the C(2)A domain of otoferlin reveals an unconventional top loop region. J Mol Biol. 2011 Feb 25;406(3):479-90. doi: 10.1016/j.jmb.2010.12.031. Epub 2011 , Jan 7. PMID:21216247 doi:http://dx.doi.org/10.1016/j.jmb.2010.12.031

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3l9b"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Rat Otoferlin C2A==
 <StructureSection load='3l9b' size='340' side='right' caption='[[3l9b]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fer1l2, Otof ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3l9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l9b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l9b RCSB], [http://www.ebi.ac.uk/pdbsum/3l9b PDBsum]</span></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=3l9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l9b OCA], [http://pdbe.org/3l9b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3l9b RCSB], [http://www.ebi.ac.uk/pdbsum/3l9b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3l9b ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3l9b" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

3l9b

From Proteopedia

Revision as of 07:31, 23 December 2016

Crystal Structure of Rat Otoferlin C2A

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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