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==Crystal Structure of RhoA.GDP.MgF3-in complex with human Myosin 9b RhoGAP domain== | |||
<StructureSection load='5hpy' size='340' side='right'caption='[[5hpy]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5hpy]] 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=5HPY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HPY 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]] 2.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</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=5hpy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hpy OCA], [https://pdbe.org/5hpy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hpy RCSB], [https://www.ebi.ac.uk/pdbsum/5hpy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hpy ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/MYO9B_HUMAN MYO9B_HUMAN] Disease susceptibility is associated with variations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MYO9B_HUMAN MYO9B_HUMAN] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. May be involved in the remodeling of the actin cytoskeleton. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions. Also acts as a GTPase activating protein on Rho. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The GTP hydrolysis activities of Rho GTPases are stimulated by GTPase-activating proteins (GAPs), which contain a RhoGAP domain equipped with a characteristic arginine finger and an auxiliary asparagine for catalysis. However, the auxiliary asparagine is missing in the RhoGAP domain of Myo9b (Myo9b-RhoGAP), a unique motorized RhoGAP that specifically targets RhoA for controlling cell motility. Here, we determined the structure of Myo9b-RhoGAP in complex with GDP-bound RhoA and magnesium fluoride. Unexpectedly, Myo9b-RhoGAP contains two arginine fingers at its catalytic site. The first arginine finger resembles the one within the canonical RhoGAP domains and inserts into the nucleotide-binding pocket of RhoA, whereas the second arginine finger anchors the Switch I loop of RhoA and interacts with the nucleotide, stabilizing the transition state of GTP hydrolysis and compensating for the lack of the asparagine. Mutating either of the two arginine fingers impaired the catalytic activity of Myo9b-RhoGAP and affected the Myo9b-mediated cell migration. Our data indicate that Myo9b-RhoGAP accelerates RhoA GTP hydrolysis by a previously unknown dual-arginine-finger mechanism, which may be shared by other noncanonical RhoGAP domains lacking the auxiliary asparagine. | |||
Noncanonical Myo9b-RhoGAP Accelerates RhoA GTP Hydrolysis by a Dual-Arginine-Finger Mechanism.,Yi F, Kong R, Ren J, Zhu L, Lou J, Wu JY, Feng W J Mol Biol. 2016 Jun 27. pii: S0022-2836(16)30222-4. doi:, 10.1016/j.jmb.2016.06.014. PMID:27363609<ref>PMID:27363609</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5hpy" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
*[[Myosin 3D Structures|Myosin 3D Structures]] | |||
*[[Rho GTPase 3D structures|Rho GTPase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Feng W]] | |||
[[Category: Ren JQ]] | |||
[[Category: Yi FS]] | |||
Latest revision as of 13:50, 16 August 2023
Crystal Structure of RhoA.GDP.MgF3-in complex with human Myosin 9b RhoGAP domainCrystal Structure of RhoA.GDP.MgF3-in complex with human Myosin 9b RhoGAP domain
Structural highlights
DiseaseMYO9B_HUMAN Disease susceptibility is associated with variations affecting the gene represented in this entry. FunctionMYO9B_HUMAN Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. May be involved in the remodeling of the actin cytoskeleton. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions. Also acts as a GTPase activating protein on Rho. Publication Abstract from PubMedThe GTP hydrolysis activities of Rho GTPases are stimulated by GTPase-activating proteins (GAPs), which contain a RhoGAP domain equipped with a characteristic arginine finger and an auxiliary asparagine for catalysis. However, the auxiliary asparagine is missing in the RhoGAP domain of Myo9b (Myo9b-RhoGAP), a unique motorized RhoGAP that specifically targets RhoA for controlling cell motility. Here, we determined the structure of Myo9b-RhoGAP in complex with GDP-bound RhoA and magnesium fluoride. Unexpectedly, Myo9b-RhoGAP contains two arginine fingers at its catalytic site. The first arginine finger resembles the one within the canonical RhoGAP domains and inserts into the nucleotide-binding pocket of RhoA, whereas the second arginine finger anchors the Switch I loop of RhoA and interacts with the nucleotide, stabilizing the transition state of GTP hydrolysis and compensating for the lack of the asparagine. Mutating either of the two arginine fingers impaired the catalytic activity of Myo9b-RhoGAP and affected the Myo9b-mediated cell migration. Our data indicate that Myo9b-RhoGAP accelerates RhoA GTP hydrolysis by a previously unknown dual-arginine-finger mechanism, which may be shared by other noncanonical RhoGAP domains lacking the auxiliary asparagine. Noncanonical Myo9b-RhoGAP Accelerates RhoA GTP Hydrolysis by a Dual-Arginine-Finger Mechanism.,Yi F, Kong R, Ren J, Zhu L, Lou J, Wu JY, Feng W J Mol Biol. 2016 Jun 27. pii: S0022-2836(16)30222-4. doi:, 10.1016/j.jmb.2016.06.014. PMID:27363609[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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