|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of the BRMS1 N-terminal region== | | ==Crystal Structure of the BRMS1 N-terminal region== |
| - | <StructureSection load='4auv' size='340' side='right' caption='[[4auv]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4auv' size='340' side='right'caption='[[4auv]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4auv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AUV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AUV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4auv]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AUV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AUV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xus|2xus]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2xus|2xus]]</div></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=4auv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4auv OCA], [http://pdbe.org/4auv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4auv RCSB], [http://www.ebi.ac.uk/pdbsum/4auv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4auv 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=4auv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4auv OCA], [https://pdbe.org/4auv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4auv RCSB], [https://www.ebi.ac.uk/pdbsum/4auv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4auv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BRMS1_HUMAN BRMS1_HUMAN]] Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down-regulates expression of anti-apoptotic genes that are controlled by NF-kappa-B. Promotes apoptosis in cells that have inadequate adherence to a substrate, a process called anoikis, and may thereby inhibit metastasis. May be a mediator of metastasis suppression in breast carcinoma.<ref>PMID:14581478</ref> <ref>PMID:17000776</ref> <ref>PMID:20830743</ref> | + | [[https://www.uniprot.org/uniprot/BRMS1_HUMAN BRMS1_HUMAN]] Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down-regulates expression of anti-apoptotic genes that are controlled by NF-kappa-B. Promotes apoptosis in cells that have inadequate adherence to a substrate, a process called anoikis, and may thereby inhibit metastasis. May be a mediator of metastasis suppression in breast carcinoma.<ref>PMID:14581478</ref> <ref>PMID:17000776</ref> <ref>PMID:20830743</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 24: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Bravo, J]] | | [[Category: Bravo, J]] |
| | [[Category: Neira, J L]] | | [[Category: Neira, J L]] |
| Structural highlights
Function
[BRMS1_HUMAN] Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down-regulates expression of anti-apoptotic genes that are controlled by NF-kappa-B. Promotes apoptosis in cells that have inadequate adherence to a substrate, a process called anoikis, and may thereby inhibit metastasis. May be a mediator of metastasis suppression in breast carcinoma.[1] [2] [3]
Publication Abstract from PubMed
The breast cancer metastasis suppressor 1 (BRMS1) gene suppresses metastasis without affecting the primary tumor growth. Cellular localization of BRMS1 appears to be important for exerting its effects on metastasis inhibition. We recently described a nucleo-cytoplasmic shuttling for BRMS1 and identified a nuclear export signal within the N-terminal coiled coil. The structure of these regions shows an antiparallel coiled coil capable of oligomerizing, which compromises the accessibility to the nuclear export signal consensus residues. We have studied the structural and biophysical features of this region to further understand the contribution of the N-terminal coiled coil to the biological function of BRMS1. We have observed that residues 85 to 98 might be important in defining the oligomerization state of the BRMS1 N-terminal coiled coil. The fragments are mainly disordered in solution, with evidence of residual structure. In addition, we report the presence of a conformational dynamic equilibrium (oligomeric folded species <--> oligomeric unfolded) in solution in the BRMS1 N-terminal coiled coil that might facilitate the nuclear export of BRMS1 to the cytoplasm.
BRMS1 and BRMS1 Are Crystal Oligomeric Coiled Coils with Different Oligomerization States, Which Behave as Disordered Protein Fragments in Solution.,Spinola-Amilibia M, Rivera J, Ortiz-Lombardia M, Romero A, Neira JL, Bravo J J Mol Biol. 2013 Mar 13. pii: S0022-2836(13)00152-6. doi:, 10.1016/j.jmb.2013.03.005. PMID:23500495[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Meehan WJ, Samant RS, Hopper JE, Carrozza MJ, Shevde LA, Workman JL, Eckert KA, Verderame MF, Welch DR. Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with retinoblastoma-binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses transcription. J Biol Chem. 2004 Jan 9;279(2):1562-9. Epub 2003 Oct 26. PMID:14581478 doi:http://dx.doi.org/10.1074/jbc.M307969200
- ↑ Liu Y, Smith PW, Jones DR. Breast cancer metastasis suppressor 1 functions as a corepressor by enhancing histone deacetylase 1-mediated deacetylation of RelA/p65 and promoting apoptosis. Mol Cell Biol. 2006 Dec;26(23):8683-96. Epub 2006 Sep 25. PMID:17000776 doi:10.1128/MCB.00940-06
- ↑ Rivera J, Megias D, Bravo J. Sorting nexin 6 interacts with breast cancer metastasis suppressor-1 and promotes transcriptional repression. J Cell Biochem. 2010 Dec 15;111(6):1464-72. doi: 10.1002/jcb.22874. PMID:20830743 doi:http://dx.doi.org/10.1002/jcb.22874
- ↑ Spinola-Amilibia M, Rivera J, Ortiz-Lombardia M, Romero A, Neira JL, Bravo J. BRMS1 and BRMS1 Are Crystal Oligomeric Coiled Coils with Different Oligomerization States, Which Behave as Disordered Protein Fragments in Solution. J Mol Biol. 2013 Mar 13. pii: S0022-2836(13)00152-6. doi:, 10.1016/j.jmb.2013.03.005. PMID:23500495 doi:10.1016/j.jmb.2013.03.005
|
