5hpy

From Proteopedia

Crystal Structure of RhoA.GDP.MgF3-in complex with human Myosin 9b RhoGAP domain

PDB ID 5hpy

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Structural highlights

5hpy 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 2.4Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MYO9B_HUMAN Disease susceptibility is associated with variations affecting the gene represented in this entry.

Function

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yi F, Kong R, Ren J, Zhu L, Lou J, Wu JY, Feng W. Noncanonical Myo9b-RhoGAP Accelerates RhoA GTP Hydrolysis by a Dual-Arginine-Finger Mechanism. J Mol Biol. 2016 Jun 27. pii: S0022-2836(16)30222-4. doi:, 10.1016/j.jmb.2016.06.014. PMID:27363609 doi:http://dx.doi.org/10.1016/j.jmb.2016.06.014