PDBsum entry 4kax

Protein binding/signaling protein

PDB id: 4kax

Contents

Protein chains

163 a.a.

143 a.a.

Ligands

GTP

CIT

GOL ×4

4IP

Metals

__K

_MG

Waters ×426

PDB id:

4kax

Name:

Protein binding/signaling protein

Title:

Crystal structure of the grp1 ph domain in complex with arf6-gtp

Structure:

Adp-ribosylation factor 6. Chain: a. Fragment: arf6 (residues 14-181). Engineered: yes. Mutation: yes. Cytohesin-3. Chain: b. Fragment: grp1 ph domain (residues 247-399). Synonym: arf nucleotide-binding site opener 3, protein arno3, general

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: arf6. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: cyth3, arno3, grp1, pscd3. Expression_system_taxid: 562

Resolution:

1.85Å R-factor: 0.202 R-free: 0.235

Authors:

D.G.Lambright,A.W.Malaby,B.Van Den Berg

Key ref:

A.W.Malaby et al. (2013). Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors. Proc Natl Acad Sci U S A, 110, 14213-14218. PubMed id: 23940353 DOI: 10.1073/pnas.1301883110

Date:

23-Apr-13 Release date: 14-Aug-13

Protein chain

P62330  (ARF6_HUMAN) -  ADP-ribosylation factor 6 from Homo sapiens

Seq: 175 a.a.

Struc: 163 a.a.*

Protein chain

O43739  (CYH3_HUMAN) -  Cytohesin-3 from Homo sapiens

Seq: 400 a.a.

Struc: 143 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chain A: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

GTP (Bound ligand (Het Group name = GTP) corresponds exactly) + H2O = GDP + phosphate + H(+)

• Enzyme class 2: Chain B: E.C.?

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: 10.1073/pnas.1301883110

Proc Natl Acad Sci U S A 110:14213-14218 (2013)

PubMed id: 23940353

Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors.

A.W.Malaby, B.van den Berg, D.G.Lambright.

ABSTRACT

Membrane recruitment of cytohesin family Arf guanine nucleotide exchange factors depends on interactions with phosphoinositides and active Arf GTPases that, in turn, relieve autoinhibition of the catalytic Sec7 domain through an unknown structural mechanism. Here, we show that Arf6-GTP relieves autoinhibition by binding to an allosteric site that includes the autoinhibitory elements in addition to the PH domain. The crystal structure of a cytohesin-3 construct encompassing the allosteric site in complex with the head group of phosphatidyl inositol 3,4,5-trisphosphate and N-terminally truncated Arf6-GTP reveals a large conformational rearrangement, whereby autoinhibition can be relieved by competitive sequestration of the autoinhibitory elements in grooves at the Arf6/PH domain interface. Disposition of the known membrane targeting determinants on a common surface is compatible with multivalent membrane docking and subsequent activation of Arf substrates, suggesting a plausible model through which membrane recruitment and allosteric activation could be structurally integrated.