9m6g
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==the crystal structure of the Ca2+/CaM-CASK-CaMK-Mint1-CID complex== | |
| + | <StructureSection load='9m6g' size='340' side='right'caption='[[9m6g]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9m6g]] is a 3 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=9M6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9M6G 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]] 1.7Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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=9m6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9m6g OCA], [https://pdbe.org/9m6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9m6g RCSB], [https://www.ebi.ac.uk/pdbsum/9m6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9m6g 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 == | ||
| + | As a member of the Ca(2+)/CaM-dependent protein kinase family, CASK contains an N-terminal CaMK domain that is regulated by Ca(2+)-bound CaM, while the underlying mechanism remains to be elucidated. Here, we determine the crystal structures of CASK-CaMK in different states: apo CASK-CaMK, CASK-CaMK in complex with CaM (the CaM-CASK complex) and CASK-CaMK in complex with CaM and Mint1 (the CaM-CASK-Mint1 complex). CASK-CaMK exhibits an inhibitory conformation with the alphaR2 helix of the autoregulatory domain (ARD) inserting into its nucleotide-binding pocket. Contrary to conventional CaM-mediated binding paradigms, in the CaM-CASK complex, only the C-terminal lobe of CaM (C-CaM) engages with the ARD of CASK-CaMK. This C-CaM binding induces the formation of an extended ARD alpha-helix that reshapes the nucleotide-binding pocket of CASK-CaMK to enhance its nucleotide-binding capacity. Correspondingly, in the CaM-CASK-Mint1 complex, similar C-CaM binding to CASK-CaMK leads to a slight opening of the CASK-Mint1 complex, and only the Mint1-CID (CASK-interaction domain) core is resolved association with CASK-CaMK. Taken together, CaM likely regulates CASK-CaMK through a C-CaM-dependent mechanism to tune its nucleotide-binding and target-recognition capacities. | ||
| - | + | Structural basis for the Ca(2+)/CaM-mediated regulation of CASK-CaMK.,Li W, Wang Y, Feng W Int J Biol Macromol. 2025 Oct 26;332(Pt 1):148495. doi: , 10.1016/j.ijbiomac.2025.148495. PMID:41151710<ref>PMID:41151710</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Li | + | <div class="pdbe-citations 9m6g" style="background-color:#fffaf0;"></div> |
| - | [[Category: Wang | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Li W]] | ||
| + | [[Category: Wang Y]] | ||
Current revision
the crystal structure of the Ca2+/CaM-CASK-CaMK-Mint1-CID complex
| |||||||||||
