PDBsum entry 5hpy

Gene regulation/signaling protein

PDB id: 5hpy

Contents

Protein chains

192 a.a.

178 a.a.

Ligands

MGF

GDP

MGF-GDP

Metals

_MG ×3

Waters ×136

PDB id:

5hpy

Name:

Gene regulation/signaling protein

Title:

Crystal structure of rhoa.Gdp.Mgf3-in complex with human myosin 9b rhogap domain

Structure:

Unconventional myosin-ixb. Chain: a, d. Synonym: unconventional myosin-9b. Engineered: yes. Transforming protein rhoa. Chain: b, f. Fragment: unp residues 3-181. Synonym: rho cdna clone 12,h12. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: myo9b, myr5. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: rhoa, arh12, arha, rho12.

Resolution:

2.40Å R-factor: 0.213 R-free: 0.246

Authors:

F.S.Yi,J.Q.Ren,W.Feng

Key ref:

F.Yi et al. (2016). Noncanonical Myo9b-RhoGAP Accelerates RhoA GTP Hydrolysis by a Dual-Arginine-Finger Mechanism. J Mol Biol, 428, 3043-3057. PubMed id: 27363609 DOI: 10.1016/j.jmb.2016.06.014

Date:

21-Jan-16 Release date: 13-Jul-16

Protein chains

Q13459  (MYO9B_HUMAN) -  Unconventional myosin-IXb from Homo sapiens

Seq: 2157 a.a.

Struc: 192 a.a.

Protein chains

P61586  (RHOA_HUMAN) -  Transforming protein RhoA from Homo sapiens

Seq: 193 a.a.

Struc: 178 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 2: Chains A, D: E.C.?
• Enzyme class 3: Chains B, F: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.jmb.2016.06.014

J Mol Biol 428:3043-3057 (2016)

PubMed id: 27363609

Noncanonical Myo9b-RhoGAP Accelerates RhoA GTP Hydrolysis by a Dual-Arginine-Finger Mechanism.

F.Yi, R.Kong, J.Ren, L.Zhu, J.Lou, J.Y.Wu, W.Feng.

ABSTRACT

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.