PDBsum entry 1e0s

G protein

PDB id: 1e0s

Contents

Protein chain

173 a.a. *

Ligands

GDP

BME

NH4

Waters ×91

* Residue conservation analysis

PDB id:

1e0s

Name:

G protein

Title:

Small g protein arf6-gdp

Structure:

Adp-ribosylation factor 6. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: arf6. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Monomer (from PDB file)

Resolution:

2.28Å R-factor: 0.172 R-free: 0.234

Authors:

J.Menetrey,J.Cherfils

Key ref:

J.Ménétrey et al. (2000). Structure of Arf6-GDP suggests a basis for guanine nucleotide exchange factors specificity. Nat Struct Biol, 7, 466-469. PubMed id: 10881192 DOI: 10.1038/75863

Date:

06-Apr-00 Release date: 18-Apr-00

Protein chain

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

Seq: 175 a.a.

Struc: 173 a.a.

Enzyme reactions

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

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

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

reference

DOI no: 10.1038/75863

Nat Struct Biol 7:466-469 (2000)

PubMed id: 10881192

Structure of Arf6-GDP suggests a basis for guanine nucleotide exchange factors specificity.

J.Ménétrey, E.Macia, S.Pasqualato, M.Franco, J.Cherfils.

ABSTRACT

Arf6 is an isoform of Arf that localizes at the periphery of the cell where it has an essential role in endocytotic pathways. Its function does not overlap with that of Arf1, although the two proteins share approximately 70% sequence identity and they have switch regions, whose conformation depends on the nature of the guanine nucleotide, with almost identical sequences. The crystal structure of Arf6-GDP at 2.3 A shows that it has a conformation similar to that of Arf1-GDP, which cannot bind membranes with high affinity. Significantly, the switch regions of Arf6 deviate by 2-5 A from those of Arf1. These differences are a consequence of the shorter N-terminal linker of Arf6 and of discrete sequence changes between Arf6 and Arf1. Mutational analysis shows that one of the positions which differs between Arf1 and Arf6 affects the configuration of the nucleotide binding site and thus the nucleotide binding properties of the Arf variant. Altogether, our results provide a structural basis for understanding how Arf1 and Arf6 can be distinguished by their guanine nucleotide exchange factors and suggest a model for the nucleotide/membrane cycle of Arf6.

Selected figure(s)

Figure 1.
Figure 1. Structure of Arf6 -GDP. a, Structure-based sequence alignment. Residues that differ between Arf1 and Arf6 are in red. b, Superposition of Arf1 -GDP14 and Arf6 -GDP. The superposition excluded the N-terminal helix and linker, the switch regions and the interswitch loop (r.m.s. deviation of C is 0.6 Å). Superimposable regions and the GDP nucleotide are in gray and are shown only for Arf6 for clarity. GDP is shown as a ball-and-stick model. Diverging regions are shown for both Arf1 and Arf6, with Arf6 in bright colors and a continuous outline, and Arf1 in pastel shades and a dotted outline. The N-terminal helix is yellow, the linker green, the switch I purple, the switch II blue and the interswitch loop red. The flexibility of the switch II in Arf1 is denoted by dashed lines. The figure was drawn with Molscript36.

Figure 2.
Figure 2. Structural changes between Arf1 and Arf6. a, Close-up view of the most divergent regions. Arf6 is shown in blue, Arf1 in white. Differences are located at the N-terminal helix, the linker, the switch I and II regions and the interswitch loop. Sequence changes important for the distinctive conformation of Arf6 are shown in red; their counterparts in Arf1 are in yellow and are labeled with an asterisk. The -strands in the interswitch region have similar conformations in Arf1 and Arf6 and are shown for Arf6 only (in gray). The orientation is as in Fig. 1b. b, Stereo view of the F[o] - F[c] electron density map near the Ser 38 -Glu 50 hydrogen bond, contoured at 3 , with shown residues omitted from the calculation.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 466-469) copyright 2000.

Figures were selected by an automated process.