3n2k

From Proteopedia

(Difference between revisions)

Current revision

TUBULIN-NSC 613862: RB3 Stathmin-like domain complex

Structural highlights

3n2k is a 5 chain structure with sequence from Ovis aries and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 4Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

STMN4_RAT Exhibits microtubule-destabilizing activity.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Tubulin is able to switch between a straight microtubule-like structure and a curved structure in complex with the stathmin-like domain of the RB3 protein (T2RB3). GTP hydrolysis following microtubule assembly induces protofilament curvature and disassembly. The conformation of the labile tubulin heterodimers is unknown. One important question is whether free GDP-tubulin dimers are straightened by GTP binding, or if GTP-tubulin is also curved and switches into a straight conformation upon assembly. We have obtained insight into the bending flexibility of tubulin by analyzing the interplay of tubulin-stathmin association with the binding of several small molecule inhibitors to the colchicine domain at the tubulin intradimer interface, combining structural and biochemical approaches. The crystal structures of T2RB3 complexes with the chiral R and S isomers of ethyl-5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl-carba mate, show that their binding site overlaps with colchicine ring A and that both complexes have the same curvature as unliganded T2RB3. The binding of these ligands is incompatible with a straight tubulin structure in microtubules. Analytical ultracentrifugation and binding measurements show that tubulin-stathmin associations (T2RB3, T2Stath) and binding of ligands (R, S, TN-16, or the colchicine analogue MTC) are thermodynamically independent from one another, irrespective of tubulin being bound to GTP or GDP. The fact that the interfacial ligands bind equally well to tubulin dimers or stathmin complexes supports a bent conformation of the free tubulin dimers. It is tempting to speculate that stathmin evolved to recognize curved structures in unassembled and disassembling tubulin, thus regulating microtubule assembly.

Stathmin and interfacial microtubule inhibitors recognize a naturally curved conformation of tubulin dimers.,Barbier P, Dorleans A, Devred F, Sanz L, Allegro D, Alfonso C, Knossow M, Peyrot V, Andreu JM J Biol Chem. 2010 Jul 30. PMID:20675373^[4]

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

References

↑ Nakao C, Itoh TJ, Hotani H, Mori N. Modulation of the stathmin-like microtubule destabilizing activity of RB3, a neuron-specific member of the SCG10 family, by its N-terminal domain. J Biol Chem. 2004 May 28;279(22):23014-21. Epub 2004 Mar 22. PMID:15039434 doi:http://dx.doi.org/10.1074/jbc.M313693200
↑ Gavet O, El Messari S, Ozon S, Sobel A. Regulation and subcellular localization of the microtubule-destabilizing stathmin family phosphoproteins in cortical neurons. J Neurosci Res. 2002 Jun 1;68(5):535-50. PMID:12111843 doi:http://dx.doi.org/10.1002/jnr.10234
↑ Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature. 2004 Mar 11;428(6979):198-202. PMID:15014504 doi:http://dx.doi.org/10.1038/nature02393
↑ Barbier P, Dorleans A, Devred F, Sanz L, Allegro D, Alfonso C, Knossow M, Peyrot V, Andreu JM. Stathmin and interfacial microtubule inhibitors recognize a naturally curved conformation of tubulin dimers. J Biol Chem. 2010 Jul 30. PMID:20675373 doi:10.1074/jbc.M110.141929

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3n2k"

@@ Line 1: / Line 1: @@
 ==TUBULIN-NSC 613862: RB3 Stathmin-like domain complex==
-<StructureSection load='3n2k' size='340' side='right' caption='[[3n2k]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
+<StructureSection load='3n2k' size='340' side='right'caption='[[3n2k]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3n2k]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N2K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3n2k]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries] 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=3N2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N2K FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=K2N:ETHYL+[(2S)-5-AMINO-2-METHYL-3-PHENYL-1,2-DIHYDROPYRIDO[3,4-B]PYRAZIN-7-YL]CARBAMATE'>K2N</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3n2g|3n2g]]</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=K2N:ETHYL+[(2S)-5-AMINO-2-METHYL-3-PHENYL-1,2-DIHYDROPYRIDO[3,4-B]PYRAZIN-7-YL]CARBAMATE'>K2N</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STMN4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</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=3n2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n2k OCA], [https://pdbe.org/3n2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n2k RCSB], [https://www.ebi.ac.uk/pdbsum/3n2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n2k ProSAT]</span></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=3n2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n2k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n2k RCSB], [http://www.ebi.ac.uk/pdbsum/3n2k PDBsum]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/STMN4_RAT STMN4_RAT] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n2/3n2k_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n2/3n2k_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3n2k ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 26: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3n2k" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Tubulin|Tubulin]]
+*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
+*[[Tubulin 3D Structures|Tubulin 3D Structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Ovis aries]]
 [[Category: Rattus norvegicus]]
-[[Category: Alfonso, C]]
+[[Category: Alfonso C]]
-[[Category: Allegro, D]]
+[[Category: Allegro D]]
-[[Category: Andreu, J M]]
+[[Category: Andreu JM]]
-[[Category: Barbier, P]]
+[[Category: Barbier P]]
-[[Category: Devred, F]]
+[[Category: Devred F]]
-[[Category: Dorleans, A]]
+[[Category: Dorleans A]]
-[[Category: Knossow, M]]
+[[Category: Knossow M]]
-[[Category: Peyrot, V]]
+[[Category: Peyrot V]]
-[[Category: Sanz, L]]
+[[Category: Sanz L]]
-[[Category: Alpha-tubulin]]
-[[Category: Beta-tubulin]]
-[[Category: Cell cycle]]
-[[Category: Colchicine domain]]
-[[Category: Covalent binding]]
-[[Category: Microtubule]]
-[[Category: Stathmin]]
-[[Category: Tubulin]]

3n2k

From Proteopedia

Current revision

TUBULIN-NSC 613862: RB3 Stathmin-like domain complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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