View source for 6kmh


==The crystal structure of CASK/Mint1 complex==
<StructureSection load='6kmh' size='340' side='right'caption='[[6kmh]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kmh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KMH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KMH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6kmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kmh OCA], [https://pdbe.org/6kmh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kmh RCSB], [https://www.ebi.ac.uk/pdbsum/6kmh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kmh ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CSKP_HUMAN CSKP_HUMAN] Defects in CASK are the cause of mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) [MIM:[https://omim.org/entry/300749 300749]. A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Patients with mental retardation X-linked CASK-related can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia. A milder phenotype consists of mental retardation alone or associated with nystagmus.<ref>PMID:19165920</ref>   Defects in CASK are the cause of FG syndrome type 4 (FGS4) [MIM:[https://omim.org/entry/300422 300422]. FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation.<ref>PMID:19200522</ref> 
== Function ==
[https://www.uniprot.org/uniprot/CSKP_HUMAN CSKP_HUMAN] Multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring and ion channel trafficking. Contributes to neural development and regulation of gene expression via interaction with the transcription factor TRB1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Calcium/calmodulin-dependent protein serine kinase (CASK) is a key player in vesicle transport and release in neurons. However, its precise role, particularly in nonneuronal systems, is incompletely understood. We report that CASK functions as an important regulator of insulin secretion. CASK depletion in mouse islets/beta cells substantially reduces insulin secretion and vesicle docking/fusion. CASK forms a ternary complex with Mint1 and Munc18-1, and this event is regulated by glucose stimulation in beta cells. The crystal structure of the CASK/Mint1 complex demonstrates that Mint1 exhibits a unique "whip"-like structure that wraps tightly around the CASK-CaMK domain, which contains dual hydrophobic interaction sites. When triggered by CASK binding, Mint1 modulates the assembly of the complex. Further investigation revealed that CASK-Mint1 binding is critical for ternary complex formation, thereby controlling Munc18-1 membrane localization and insulin secretion. Our work illustrates the distinctive molecular basis underlying CASK/Mint1/Munc18-1 complex formation and reveals the importance of the CASK-Mint1-Munc18 signaling axis in insulin secretion.

CASK modulates the assembly and function of the Mint1/Munc18-1 complex to regulate insulin secretion.,Zhang Z, Li W, Yang G, Lu X, Qi X, Wang S, Cao C, Zhang P, Ren J, Zhao J, Zhang J, Hong S, Tan Y, Burchfield J, Yu Y, Xu T, Yao X, James D, Feng W, Chen Z Cell Discov. 2020 Dec 15;6(1):92. doi: 10.1038/s41421-020-00216-3. PMID:33318489<ref>PMID:33318489</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6kmh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Feng W]]
[[Category: Li W]]