View source for 6rev


==Cryo-EM structure of the N-terminal DC repeat (NDC) of human doublecortin (DCX) bound to 13-protofilament GDP-microtubule==
<StructureSection load='6rev' size='340' side='right'caption='[[6rev]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rev]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6REV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6REV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6rev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rev OCA], [https://pdbe.org/6rev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rev RCSB], [https://www.ebi.ac.uk/pdbsum/6rev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rev ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/DCX_HUMAN DCX_HUMAN] Defects in DCX are the cause of lissencephaly X-linked type 1 (LISX1) [MIM:[https://omim.org/entry/300067 300067]; also called X-LIS or LIS. LISX1 is a classic lissencephaly characterized by mental retardation and seizures that are more severe in male patients. Affected boys show an abnormally thick cortex with absent or severely reduced gyri. Clinical manifestations include feeding problems, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe phenotype referred to as 'doublecortex'.<ref>PMID:9489699</ref> <ref>PMID:9489700</ref> <ref>PMID:9668176</ref> <ref>PMID:9817918</ref> <ref>PMID:11468322</ref> <ref>PMID:12552055</ref>   Defects in DCX are the cause of subcortical band heterotopia X-linked (SBHX) [MIM:[https://omim.org/entry/300067 300067]; also known as double cortex or subcortical laminar heterotopia (SCLH). SBHX is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal.<ref>PMID:9618162</ref> <ref>PMID:9989615</ref> <ref>PMID:10369164</ref> <ref>PMID:10441340</ref> <ref>PMID:10807542</ref> <ref>PMID:11601509</ref> <ref>PMID:11175293</ref> <ref>PMID:12390976</ref>   Note=A chromosomal aberration involving DCX is found in lissencephaly. Translocation t(X;2)(q22.3;p25.1).
== Function ==
[https://www.uniprot.org/uniprot/DCX_HUMAN DCX_HUMAN] Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. May act by competing with the putative neuronal protein kinase DCLK1 in binding to a target protein. May in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. May be part with PAFAH1B1/LIS-1 of overlapping, but distinct, signaling pathways that promote neuronal migration.<ref>PMID:22359282</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Doublecortin (DCX) is a neuronal microtubule-associated protein (MAP) indispensable for brain development. Its flexibly linked doublecortin (DC) domains-NDC and CDC-mediate microtubule (MT) nucleation and stabilization, but it is unclear how. Using high-resolution time-resolved cryo-EM, we mapped NDC and CDC interactions with tubulin at different MT polymerization stages and studied their functional effects on MT dynamics using TIRF microscopy. Although coupled, each DC repeat within DCX appears to have a distinct role in MT nucleation and stabilization: CDC is a conformationally plastic module that appears to facilitate MT nucleation and stabilize tubulin-tubulin contacts in the nascent MT lattice, while NDC appears to be favored along the mature lattice, providing MT stabilization. Our structures of MT-bound DC domains also explain in unprecedented detail the DCX mutation-related brain defects observed in the clinic. This modular composition of DCX reflects a common design principle among MAPs where pseudo-repeats of tubulin/MT binding elements chaperone or stabilize distinct conformational transitions to regulate distinct stages of MT dynamic instability.

Pseudo-repeats in doublecortin make distinct mechanistic contributions to microtubule regulation.,Manka SW, Moores CA EMBO Rep. 2020 Oct 14:e51534. doi: 10.15252/embr.202051534. PMID:33051979<ref>PMID:33051979</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6rev" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Manka SW]]