|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Structure of the murine Nore1-Sarah domain== | | ==Structure of the murine Nore1-Sarah domain== |
| - | <StructureSection load='2ymy' size='340' side='right' caption='[[2ymy]], [[Resolution|resolution]] 1.69Å' scene=''> | + | <StructureSection load='2ymy' size='340' side='right'caption='[[2ymy]], [[Resolution|resolution]] 1.69Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ymy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YMY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YMY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ymy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YMY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YMY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</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]] 1.69Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fnf|2fnf]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</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=2ymy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ymy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ymy RCSB], [http://www.ebi.ac.uk/pdbsum/2ymy PDBsum]</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=2ymy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ymy OCA], [https://pdbe.org/2ymy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ymy RCSB], [https://www.ebi.ac.uk/pdbsum/2ymy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ymy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RASF5_MOUSE RASF5_MOUSE]] Potental tumor suppressor. Seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. Isoform 2 stimulates lymphocyte polarization and the patch-like distribution of ITGAL/LFA-1, resulting in an enhanced adhesion to ICAM1. Together with RAP1A may participate in regulation of microtubule growth. The association of isoform 2 with activated RAP1A is required for directional movement of endothelial cells during wound healing (By similarity). May be involved in regulation of Ras apoptotic function. The RASSF5-STK4/MST1 complex may mediate HRAS1 and KRAS induced apoptosis.<ref>PMID:11864565</ref> | + | [https://www.uniprot.org/uniprot/RASF5_MOUSE RASF5_MOUSE] Potental tumor suppressor. Seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. Isoform 2 stimulates lymphocyte polarization and the patch-like distribution of ITGAL/LFA-1, resulting in an enhanced adhesion to ICAM1. Together with RAP1A may participate in regulation of microtubule growth. The association of isoform 2 with activated RAP1A is required for directional movement of endothelial cells during wound healing (By similarity). May be involved in regulation of Ras apoptotic function. The RASSF5-STK4/MST1 complex may mediate HRAS1 and KRAS induced apoptosis.<ref>PMID:11864565</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 17: |
Line 18: |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2ymy" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Aruxandei, D C]] | + | [[Category: Mus musculus]] |
| - | [[Category: Herrmann, C]] | + | [[Category: Aruxandei DC]] |
| - | [[Category: Hofmann, E]] | + | [[Category: Herrmann C]] |
| - | [[Category: Makbul, C]] | + | [[Category: Hofmann E]] |
| - | [[Category: Schwarz, D]] | + | [[Category: Makbul C]] |
| - | [[Category: Wolf, E]] | + | [[Category: Schwarz D]] |
| - | [[Category: Apoptosis]]
| + | [[Category: Wolf E]] |
| - | [[Category: Coiled-coil]]
| + | |
| - | [[Category: Ras association domain family]]
| + | |
| - | [[Category: Tumor suppressor]]
| + | |
| Structural highlights
Function
RASF5_MOUSE Potental tumor suppressor. Seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. Isoform 2 stimulates lymphocyte polarization and the patch-like distribution of ITGAL/LFA-1, resulting in an enhanced adhesion to ICAM1. Together with RAP1A may participate in regulation of microtubule growth. The association of isoform 2 with activated RAP1A is required for directional movement of endothelial cells during wound healing (By similarity). May be involved in regulation of Ras apoptotic function. The RASSF5-STK4/MST1 complex may mediate HRAS1 and KRAS induced apoptosis.[1]
Publication Abstract from PubMed
Tumor suppressor Nore1, its acronym coming from novel Ras effector, is one of the 10 members of the Rassf (Ras association domain family) protein family that have been identified. It is expressed as two mRNA splice variants, Nore1A and a shorter isoform, Nore1B. It forms homo- and heterocomplexes through its C-terminal SARAH (Sav/Rassf/Hpo) domain. The oligomeric state of Nore1 and other SARAH domain-containing proteins is important for their cellular activities. However, there are few experimental data addressing the structural and biophysical characterization of these domains. In this study, we show that the recombinant SARAH domain of Nore1 crystallizes as an antiparallel homodimer with representative characteristics of coiled coils. As is typical for coiled coils, the SARAH domain shows a heptad register, yet the heptad register is interrupted by two stutters. The comparisons of the heptad register of Nore1-SARAH with the primary structure of Rassf1-4, Rassf6, MST1, MST2, and WW45 indicate that these proteins have a heptad register interrupted by two stutters, too. Moreover, on the basis of the structure of Nore1-SARAH, we also generate structural models for Rassf1 and Rassf3. These models indicate that Rassf1- and Rassf3-SARAH form structures very similar to that of Nore1-SARAH. In addition, we show that, as we have previously found for MST1, the SARAH domain of Nore1 undergoes association-dependent folding. Nevertheless, the Nore1 homodimer has a lower affinity and thermodynamic stability than the MST1 homodimer, while the monomer is slightly more stable. Our experimental results along with our theoretical considerations indicate that the SARAH domain is merely a dimerization domain and that the differences between the individual sequences lead to different stabilities and affinities that might have an important functional role.
Structural and Thermodynamic Characterization of Nore1-SARAH: A Small, Helical Module Important in Signal Transduction Networks.,Makbul C, Constantinescu Aruxandei D, Hofmann E, Schwarz D, Wolf E, Herrmann C Biochemistry. 2013 Feb 12;52(6):1045-54. doi: 10.1021/bi3014642. Epub 2013 Jan, 30. PMID:23331050[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T, Zhang XF, Seed B, Avruch J. Identification of a novel Ras-regulated proapoptotic pathway. Curr Biol. 2002 Feb 19;12(4):253-65. PMID:11864565
- ↑ Makbul C, Constantinescu Aruxandei D, Hofmann E, Schwarz D, Wolf E, Herrmann C. Structural and Thermodynamic Characterization of Nore1-SARAH: A Small, Helical Module Important in Signal Transduction Networks. Biochemistry. 2013 Feb 12;52(6):1045-54. doi: 10.1021/bi3014642. Epub 2013 Jan, 30. PMID:23331050 doi:http://dx.doi.org/10.1021/bi3014642
|
