6rf2: Difference between revisions

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<StructureSection load='6rf2' size='340' side='right'caption='[[6rf2]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
<StructureSection load='6rf2' size='340' side='right'caption='[[6rf2]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6rf2]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RF2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RF2 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6rf2]] 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=6RF2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RF2 FirstGlance]. <br>
</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>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCX, DBCN, LISX ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6rf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rf2 OCA], [https://pdbe.org/6rf2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rf2 RCSB], [https://www.ebi.ac.uk/pdbsum/6rf2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rf2 ProSAT]</span></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=6rf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rf2 OCA], [https://pdbe.org/6rf2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rf2 RCSB], [https://www.ebi.ac.uk/pdbsum/6rf2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rf2 ProSAT]</span></td></tr>
</table>
</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 ==
== Function ==
[[https://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. [[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>  [[https://www.uniprot.org/uniprot/TBB2B_BOVIN TBB2B_BOVIN]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).  
[https://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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</StructureSection>
</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Manka, S W]]
[[Category: Manka SW]]
[[Category: Cytosolic protein]]
[[Category: Microtubule nucleation and stabilisation]]
[[Category: Microtubule-associated protein]]
[[Category: Neuronal migration protein]]

Latest revision as of 13:11, 22 May 2024

Cryo-EM structure of the C-terminal DC repeat (CDC) of human doublecortin (DCX) bound to 13-protofilament GDP.Pi-microtubuleCryo-EM structure of the C-terminal DC repeat (CDC) of human doublecortin (DCX) bound to 13-protofilament GDP.Pi-microtubule

Structural highlights

6rf2 is a 5 chain structure with sequence from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 4.2Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TBA1B_BOVIN Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.

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[1]

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

See Also

References

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

6rf2, resolution 4.20Å

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