6cdf

From Proteopedia

(Difference between revisions)

Revision as of 06:17, 9 May 2018

Human CtBP1 (28-378)

Structural highlights

6cdf is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CTBP1_HUMAN] Involved in controlling the equilibrium between tubular and stacked structures in the Golgi complex. Functions in brown adipose tissue (BAT) differentiation. Corepressor targeting diverse transcription regulators such as GLIS2. Has dehydrogenase activity.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

C-terminal binding protein 1 (CtBP1) and CtBP2 are transcriptional coregulators that repress numerous cellular processes, such as apoptosis, by binding transcription factors and recruiting chromatin-remodeling enzymes to gene promoters. The NAD(H) linked oligomerization of human CtBP is coupled to its co-transcriptional activity, which is implicated in cancer progression. However, the biologically relevant level of CtBP assembly has not been firmly established, nor has the stereochemical arrangement of the subunits above that of a dimer. Here, multi-angle light scattering (MALS) data established the NAD+and NADH-dependent assembly of CtBP1 and CtBP2 into tetramers. An examination of subunit interactions within CtBP1 and CtBP2 crystal lattices revealed that both share a very similar tetrameric arrangement resulting from assembly of two dimeric pairs, with specific interactions likely being sensitive to NAD(H) binding. Creating a series of mutants of both CtBP1 and CtBP2, we tested the hypothesis that the crystallographically observed interdimer pairing stabilizes the solution tetramer. MALS data confirmed that these mutants disrupt both CtBP1 and CtBP2 tetramers, with the dimer generally remaining intact, providing the first stereochemical models for tetrameric assemblies of CtBP1 and CtBP2. The crystal structure of a subtle destabilizing mutant suggested that small structural perturbations of the hinge region linking the substrate- and NAD-binding domains are sufficient to weaken the CtBP1 tetramer. These results strongly suggest that the tetramer is important in CtBP function and the series of CtBP mutants reported here can be used to investigate the physiological role of the tetramer.

Assembly of human C-terminal Binding Protein (CtBP) into tetramers.,Bellesis AG, Jecrois AM, Hayes JA, Schiffer C, Royer WE Jr. J Biol Chem. 2018 Apr 26. pii: RA118.002514. doi: 10.1074/jbc.RA118.002514. PMID:29700119^[5]

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

References

↑ Sewalt RG, Gunster MJ, van der Vlag J, Satijn DP, Otte AP. C-Terminal binding protein is a transcriptional repressor that interacts with a specific class of vertebrate Polycomb proteins. Mol Cell Biol. 1999 Jan;19(1):777-87. PMID:9858600
↑ Alpatov R, Munguba GC, Caton P, Joo JH, Shi Y, Shi Y, Hunt ME, Sugrue SP. Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene. Mol Cell Biol. 2004 Dec;24(23):10223-35. PMID:15542832 doi:http://dx.doi.org/10.1128/MCB.24.23.10223-10235.2004
↑ Purbey PK, Singh S, Notani D, Kumar PP, Limaye AS, Galande S. Acetylation-dependent interaction of SATB1 and CtBP1 mediates transcriptional repression by SATB1. Mol Cell Biol. 2009 Mar;29(5):1321-37. doi: 10.1128/MCB.00822-08. Epub 2008 Dec, 22. PMID:19103759 doi:10.1128/MCB.00822-08
↑ Kumar V, Carlson JE, Ohgi KA, Edwards TA, Rose DW, Escalante CR, Rosenfeld MG, Aggarwal AK. Transcription corepressor CtBP is an NAD(+)-regulated dehydrogenase. Mol Cell. 2002 Oct;10(4):857-69. PMID:12419229
↑ Bellesis AG, Jecrois AM, Hayes JA, Schiffer C, Royer WE Jr.. Assembly of human C-terminal Binding Protein (CtBP) into tetramers. J Biol Chem. 2018 Apr 26. pii: RA118.002514. doi: 10.1074/jbc.RA118.002514. PMID:29700119 doi:http://dx.doi.org/10.1074/jbc.RA118.002514

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6cdf"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6cdf is ON HOLD  until Paper Publication
+==Human CtBP1 (28-378)==
+<StructureSection load='6cdf' size='340' side='right' caption='[[6cdf]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6cdf]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CDF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CDF FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</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=6cdf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cdf OCA], [http://pdbe.org/6cdf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cdf RCSB], [http://www.ebi.ac.uk/pdbsum/6cdf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cdf ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/CTBP1_HUMAN CTBP1_HUMAN]] Involved in controlling the equilibrium between tubular and stacked structures in the Golgi complex. Functions in brown adipose tissue (BAT) differentiation. Corepressor targeting diverse transcription regulators such as GLIS2. Has dehydrogenase activity.<ref>PMID:9858600</ref> <ref>PMID:15542832</ref> <ref>PMID:19103759</ref> <ref>PMID:12419229</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+C-terminal binding protein 1 (CtBP1) and CtBP2 are transcriptional coregulators that repress numerous cellular processes, such as apoptosis, by binding transcription factors and recruiting chromatin-remodeling enzymes to gene promoters. The NAD(H) linked oligomerization of human CtBP is coupled to its co-transcriptional activity, which is implicated in cancer progression. However, the biologically relevant level of CtBP assembly has not been firmly established, nor has the stereochemical arrangement of the subunits above that of a dimer. Here, multi-angle light scattering (MALS) data established the NAD+and NADH-dependent assembly of CtBP1 and CtBP2 into tetramers. An examination of subunit interactions within CtBP1 and CtBP2 crystal lattices revealed that both share a very similar tetrameric arrangement resulting from assembly of two dimeric pairs, with specific interactions likely being sensitive to NAD(H) binding. Creating a series of mutants of both CtBP1 and CtBP2, we tested the hypothesis that the crystallographically observed interdimer pairing stabilizes the solution tetramer. MALS data confirmed that these mutants disrupt both CtBP1 and CtBP2 tetramers, with the dimer generally remaining intact, providing the first stereochemical models for tetrameric assemblies of CtBP1 and CtBP2. The crystal structure of a subtle destabilizing mutant suggested that small structural perturbations of the hinge region linking the substrate- and NAD-binding domains are sufficient to weaken the CtBP1 tetramer. These results strongly suggest that the tetramer is important in CtBP function and the series of CtBP mutants reported here can be used to investigate the physiological role of the tetramer.
-Authors: Royer, W.E., Bellesis, A.G.
+Assembly of human C-terminal Binding Protein (CtBP) into tetramers.,Bellesis AG, Jecrois AM, Hayes JA, Schiffer C, Royer WE Jr. J Biol Chem. 2018 Apr 26. pii: RA118.002514. doi: 10.1074/jbc.RA118.002514. PMID:29700119<ref>PMID:29700119</ref>
-Description: Human CtBP1 (28-378)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Bellesis, A.G]]
+<div class="pdbe-citations 6cdf" style="background-color:#fffaf0;"></div>
-[[Category: Royer, W.E]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Bellesis, A G]]
+[[Category: Royer, W E]]
+[[Category: Cancer target]]
+[[Category: Ctbp]]
+[[Category: Nadh]]
+[[Category: Transcription]]

6cdf

From Proteopedia

Revision as of 06:17, 9 May 2018

Human CtBP1 (28-378)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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