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The entry | ==Crystal structure of CPAP PN2-3 C-terminal loop-helix in complex with DARPin-tubulin== | ||
<StructureSection load='5eib' size='340' side='right' caption='[[5eib]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5eib]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EIB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EIB FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5eib FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eib OCA], [http://pdbe.org/5eib PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eib RCSB], [http://www.ebi.ac.uk/pdbsum/5eib PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eib ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/CENPJ_HUMAN CENPJ_HUMAN]] Seckel syndrome;Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/CENPJ_HUMAN CENPJ_HUMAN]] Plays an important role in cell division and centrosome function by participating in centriole duplication. Inhibits microtubule nucleation from the centrosome.<ref>PMID:15047868</ref> <ref>PMID:17681131</ref> <ref>PMID:20531387</ref> [[http://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. [[http://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). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Centrioles and cilia are microtubule-based structures, whose precise formation requires controlled cytoplasmic tubulin incorporation. How cytoplasmic tubulin is recognized for centriolar/ciliary-microtubule construction remains poorly understood. Centrosomal-P4.1-associated-protein (CPAP) binds tubulin via its PN2-3 domain. Here, we show that a C-terminal loop-helix in PN2-3 targets beta-tubulin at the microtubule outer surface, while an N-terminal helical motif caps microtubule's alpha-beta surface of beta-tubulin. Through this, PN2-3 forms a high-affinity complex with GTP-tubulin, crucial for defining numbers and lengths of centriolar/ciliary-microtubules. Surprisingly, two distinct mutations in PN2-3 exhibit opposite effects on centriolar/ciliary-microtubule lengths. CPAP(F375A), with strongly reduced tubulin interaction, causes shorter centrioles and cilia exhibiting doublet- instead of triplet-microtubules. CPAP(EE343RR) that unmasks the beta-tubulin polymerization surface displays slightly reduced tubulin-binding affinity inducing over-elongation of newly forming centriolar/ciliary-microtubules by enhanced dynamic release of its bound tubulin. Thus CPAP regulates delivery of its bound-tubulin to define the size of microtubule-based cellular structures using a 'clutch-like' mechanism. | |||
Molecular basis for CPAP-tubulin interaction in controlling centriolar and ciliary length.,Zheng X, Ramani A, Soni K, Gottardo M, Zheng S, Ming Gooi L, Li W, Feng S, Mariappan A, Wason A, Widlund P, Pozniakovsky A, Poser I, Deng H, Ou G, Riparbelli M, Giuliano C, Hyman AA, Sattler M, Gopalakrishnan J, Li H Nat Commun. 2016 Jun 16;7:11874. doi: 10.1038/ncomms11874. PMID:27306797<ref>PMID:27306797</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5eib" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Li, H]] | |||
[[Category: Zheng, X]] | [[Category: Zheng, X]] | ||
[[Category: | [[Category: Cell cycle]] | ||
[[Category: Pn2-3]] | |||
[[Category: Tubulin complex]] | |||
Revision as of 21:30, 26 October 2016
Crystal structure of CPAP PN2-3 C-terminal loop-helix in complex with DARPin-tubulinCrystal structure of CPAP PN2-3 C-terminal loop-helix in complex with DARPin-tubulin
Structural highlights
Disease[CENPJ_HUMAN] Seckel syndrome;Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function[CENPJ_HUMAN] Plays an important role in cell division and centrosome function by participating in centriole duplication. Inhibits microtubule nucleation from the centrosome.[1] [2] [3] [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. [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). Publication Abstract from PubMedCentrioles and cilia are microtubule-based structures, whose precise formation requires controlled cytoplasmic tubulin incorporation. How cytoplasmic tubulin is recognized for centriolar/ciliary-microtubule construction remains poorly understood. Centrosomal-P4.1-associated-protein (CPAP) binds tubulin via its PN2-3 domain. Here, we show that a C-terminal loop-helix in PN2-3 targets beta-tubulin at the microtubule outer surface, while an N-terminal helical motif caps microtubule's alpha-beta surface of beta-tubulin. Through this, PN2-3 forms a high-affinity complex with GTP-tubulin, crucial for defining numbers and lengths of centriolar/ciliary-microtubules. Surprisingly, two distinct mutations in PN2-3 exhibit opposite effects on centriolar/ciliary-microtubule lengths. CPAP(F375A), with strongly reduced tubulin interaction, causes shorter centrioles and cilia exhibiting doublet- instead of triplet-microtubules. CPAP(EE343RR) that unmasks the beta-tubulin polymerization surface displays slightly reduced tubulin-binding affinity inducing over-elongation of newly forming centriolar/ciliary-microtubules by enhanced dynamic release of its bound tubulin. Thus CPAP regulates delivery of its bound-tubulin to define the size of microtubule-based cellular structures using a 'clutch-like' mechanism. Molecular basis for CPAP-tubulin interaction in controlling centriolar and ciliary length.,Zheng X, Ramani A, Soni K, Gottardo M, Zheng S, Ming Gooi L, Li W, Feng S, Mariappan A, Wason A, Widlund P, Pozniakovsky A, Poser I, Deng H, Ou G, Riparbelli M, Giuliano C, Hyman AA, Sattler M, Gopalakrishnan J, Li H Nat Commun. 2016 Jun 16;7:11874. doi: 10.1038/ncomms11874. PMID:27306797[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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