1s1c: Difference between revisions

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New page: left|200px<br /> <applet load="1s1c" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s1c, resolution 2.60Å" /> '''Crystal structure o...
 
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[[Image:1s1c.gif|left|200px]]<br />
<applet load="1s1c" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1s1c, resolution 2.60&Aring;" />
'''Crystal structure of the complex between the human RhoA and Rho-binding domain of human ROCKI'''<br />


==Overview==
==Crystal structure of the complex between the human RhoA and Rho-binding domain of human ROCKI==
The Rho-ROCK pathway modulates the phosphorylation level of a variety of, important signaling proteins and is thereby involved in miscellaneous, cellular processes including cell migration, neurite outgrowth, and smooth, muscle contraction. The observation of the involvement of the Rho-ROCK, pathway in tumor invasion and in diseases such as hypertension and, bronchial asthma makes it an interesting target for drug development. We, herein present the crystal structure of the complex between active RhoA, and the Rho-binding domain of ROCKI. The Rho-binding domain structure, forms a parallel alpha-helical coiled-coil dimer and, in contrast to the, published Rho-protein kinase N structure, binds exclusively to the switch, I and II regions of the guanosine 5'-(beta,gamma-imido)triphosphate-bound, RhoA. The switch regions of two different RhoA molecules form a, predominantly hydrophobic patch, which is complementarily bound by two, identical short helices of 13 residues (amino acids 998-1010). The, identified ROCK-binding site of RhoA strikingly supports the assumption of, a common consensus-binding site for effector recognition.
<StructureSection load='1s1c' size='340' side='right'caption='[[1s1c]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1s1c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S1C FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=1s1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s1c OCA], [https://pdbe.org/1s1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s1c RCSB], [https://www.ebi.ac.uk/pdbsum/1s1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s1c ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RHOA_HUMAN RHOA_HUMAN] Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization.<ref>PMID:8910519</ref> <ref>PMID:9121475</ref> <ref>PMID:12900402</ref> <ref>PMID:16103226</ref> <ref>PMID:16236794</ref> <ref>PMID:19934221</ref> <ref>PMID:20937854</ref> <ref>PMID:20974804</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/s1/1s1c_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/main_output.php?pdb_ID=1s1c ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1S1C is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and GNP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S1C OCA].
*[[Rho GTPase 3D structures|Rho GTPase 3D structures]]
 
*[[Rho-associated protein kinase 3D structures|Rho-associated protein kinase 3D structures]]
==Reference==
== References ==
Structural insights into the interaction of ROCKI with the switch regions of RhoA., Dvorsky R, Blumenstein L, Vetter IR, Ahmadian MR, J Biol Chem. 2004 Feb 20;279(8):7098-104. Epub 2003 Dec 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14660612 14660612]
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Ahmadian, M.R.]]
[[Category: Ahmadian MR]]
[[Category: Blumenstein, L.]]
[[Category: Blumenstein L]]
[[Category: Dvorsky, R.]]
[[Category: Dvorsky R]]
[[Category: Vetter, I.R.]]
[[Category: Vetter IR]]
[[Category: GNP]]
[[Category: MG]]
[[Category: coiled-coil]]
[[Category: gtpase]]
[[Category: rho kinase]]
[[Category: rock]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:09:13 2007''

Latest revision as of 11:27, 14 February 2024

Crystal structure of the complex between the human RhoA and Rho-binding domain of human ROCKICrystal structure of the complex between the human RhoA and Rho-binding domain of human ROCKI

Structural highlights

1s1c is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RHOA_HUMAN Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization.[1] [2] [3] [4] [5] [6] [7] [8]

Evolutionary Conservation

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

See Also

References

  1. ↑ Quilliam LA, Lambert QT, Mickelson-Young LA, Westwick JK, Sparks AB, Kay BK, Jenkins NA, Gilbert DJ, Copeland NG, Der CJ. Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling. J Biol Chem. 1996 Nov 15;271(46):28772-6. PMID:8910519
  2. ↑ Vincent S, Settleman J. The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization. Mol Cell Biol. 1997 Apr;17(4):2247-56. PMID:9121475
  3. ↑ Wing MR, Snyder JT, Sondek J, Harden TK. Direct activation of phospholipase C-epsilon by Rho. J Biol Chem. 2003 Oct 17;278(42):41253-8. Epub 2003 Aug 4. PMID:12900402 doi:http://dx.doi.org/10.1074/jbc.M306904200
  4. ↑ Yuce O, Piekny A, Glotzer M. An ECT2-centralspindlin complex regulates the localization and function of RhoA. J Cell Biol. 2005 Aug 15;170(4):571-82. PMID:16103226 doi:10.1083/jcb.200501097
  5. ↑ Kamijo K, Ohara N, Abe M, Uchimura T, Hosoya H, Lee JS, Miki T. Dissecting the role of Rho-mediated signaling in contractile ring formation. Mol Biol Cell. 2006 Jan;17(1):43-55. Epub 2005 Oct 19. PMID:16236794 doi:10.1091/mbc.E05-06-0569
  6. ↑ Bristow JM, Sellers MH, Majumdar D, Anderson B, Hu L, Webb DJ. The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin dynamics and thereby regulate cell migration. J Cell Sci. 2009 Dec 15;122(Pt 24):4535-46. doi: 10.1242/jcs.053728. Epub 2009, Nov 24. PMID:19934221 doi:10.1242/jcs.053728
  7. ↑ Zaoui K, Benseddik K, Daou P, Salaun D, Badache A. ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18517-22. doi:, 10.1073/pnas.1000975107. Epub 2010 Oct 11. PMID:20937854 doi:10.1073/pnas.1000975107
  8. ↑ Wallace SW, Magalhaes A, Hall A. The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells. Mol Cell Biol. 2011 Jan;31(1):81-91. doi: 10.1128/MCB.01001-10. Epub 2010 Oct 25. PMID:20974804 doi:10.1128/MCB.01001-10

1s1c, resolution 2.60Å

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