|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Structure of FLIN2, a complex containing the N-terminal LIM domain of LMO2 and ldb1-LID== | | ==Structure of FLIN2, a complex containing the N-terminal LIM domain of LMO2 and ldb1-LID== |
| - | <StructureSection load='1j2o' size='340' side='right' caption='[[1j2o]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1j2o' size='340' side='right'caption='[[1j2o]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1j2o]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J2O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1J2O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1j2o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J2O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1J2O FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1m3v|1m3v]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LMO2, Ldb1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=1j2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j2o OCA], [https://pdbe.org/1j2o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1j2o RCSB], [https://www.ebi.ac.uk/pdbsum/1j2o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1j2o 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=1j2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j2o OCA], [http://pdbe.org/1j2o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1j2o RCSB], [http://www.ebi.ac.uk/pdbsum/1j2o PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RBTN2_MOUSE RBTN2_MOUSE]] Acts with TAL1/SCL to regulate red blood cell development. Also acts with LDB1 to maintain erythroid precursors in an immature state.<ref>PMID:9391090</ref> | + | [https://www.uniprot.org/uniprot/LDB1_MOUSE LDB1_MOUSE] Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. May play a role in the development of motor neurons. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state.<ref>PMID:8918878</ref> <ref>PMID:8876198</ref> <ref>PMID:9192866</ref> <ref>PMID:9391090</ref> <ref>PMID:16815859</ref> <ref>PMID:9315627</ref> [https://www.uniprot.org/uniprot/RBTN2_MOUSE RBTN2_MOUSE] Acts with TAL1/SCL to regulate red blood cell development. Also acts with LDB1 to maintain erythroid precursors in an immature state.<ref>PMID:9391090</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j2/1j2o_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j2/1j2o_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| Line 33: |
Line 33: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Deane, J E]] | + | [[Category: Mus musculus]] |
| - | [[Category: Kwan, A H]] | + | [[Category: Deane JE]] |
| - | [[Category: Mackay, J P]] | + | [[Category: Kwan AH]] |
| - | [[Category: Matthews, J M]] | + | [[Category: Mackay JP]] |
| - | [[Category: Sum, E Y]] | + | [[Category: Matthews JM]] |
| - | [[Category: Visvader, J E]] | + | [[Category: Sum EY]] |
| - | [[Category: Lim domain]] | + | [[Category: Visvader JE]] |
| - | [[Category: Metal binding protein]]
| + | |
| Structural highlights
Function
LDB1_MOUSE Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. May play a role in the development of motor neurons. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state.[1] [2] [3] [4] [5] [6] RBTN2_MOUSE Acts with TAL1/SCL to regulate red blood cell development. Also acts with LDB1 to maintain erythroid precursors in an immature state.[7]
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
LMO2 and LMO4 are members of a small family of nuclear transcriptional regulators that are important for both normal development and disease processes. LMO2 is essential for hemopoiesis and angiogenesis, and inappropriate overexpression of this protein leads to T-cell leukemias. LMO4 is developmentally regulated in the mammary gland and has been implicated in breast oncogenesis. Both proteins comprise two tandemly repeated LIM domains. LMO2 and LMO4 interact with the ubiquitous nuclear adaptor protein ldb1/NLI/CLIM2, which associates with the LIM domains of LMO and LIM homeodomain proteins via its LIM interaction domain (ldb1-LID). We report the solution structures of two LMO:ldb1 complexes (PDB: 1M3V and 1J2O) and show that ldb1-LID binds to the N-terminal LIM domain (LIM1) of LMO2 and LMO4 in an extended conformation, contributing a third strand to a beta-hairpin in LIM1 domains. These findings constitute the first molecular definition of LIM-mediated protein-protein interactions and suggest a mechanism by which ldb1 can bind a variety of LIM domains that share low sequence homology.
Structural basis for the recognition of ldb1 by the N-terminal LIM domains of LMO2 and LMO4.,Deane JE, Mackay JP, Kwan AH, Sum EY, Visvader JE, Matthews JM EMBO J. 2003 May 1;22(9):2224-33. PMID:12727888[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Agulnick AD, Taira M, Breen JJ, Tanaka T, Dawid IB, Westphal H. Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins. Nature. 1996 Nov 21;384(6606):270-2. PMID:8918878 doi:http://dx.doi.org/10.1038/384270a0
- ↑ Jurata LW, Kenny DA, Gill GN. Nuclear LIM interactor, a rhombotin and LIM homeodomain interacting protein, is expressed early in neuronal development. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11693-8. PMID:8876198
- ↑ Bach I, Carriere C, Ostendorff HP, Andersen B, Rosenfeld MG. A family of LIM domain-associated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins. Genes Dev. 1997 Jun 1;11(11):1370-80. PMID:9192866
- ↑ Visvader JE, Mao X, Fujiwara Y, Hahm K, Orkin SH. The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13707-12. PMID:9391090
- ↑ Tran YH, Xu Z, Kato A, Mistry AC, Goya Y, Taira M, Brandt SJ, Hirose S. Spliced isoforms of LIM-domain-binding protein (CLIM/NLI/Ldb) lacking the LIM-interaction domain. J Biochem. 2006 Jul;140(1):105-19. Epub 2006 Jun 30. PMID:16815859 doi:http://dx.doi.org/10.1093/jb/mvj134
- ↑ Jurata LW, Gill GN. Functional analysis of the nuclear LIM domain interactor NLI. Mol Cell Biol. 1997 Oct;17(10):5688-98. PMID:9315627
- ↑ Visvader JE, Mao X, Fujiwara Y, Hahm K, Orkin SH. The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13707-12. PMID:9391090
- ↑ Deane JE, Mackay JP, Kwan AH, Sum EY, Visvader JE, Matthews JM. Structural basis for the recognition of ldb1 by the N-terminal LIM domains of LMO2 and LMO4. EMBO J. 2003 May 1;22(9):2224-33. PMID:12727888 doi:10.1093/emboj/cdg196
|
