ADP ribosylation factor


ADP ribosylation factor

Pfam_box
Symbol = Arf
Name =



width =250
caption =Membrane-bound ADP ribosylation factor-like protein 2 (ARL2 mouse, red), complex with phosphodiesterase delta (yellow) (PDB3|1ksg) Blue dots show hydrocarbon boundary of the lipid bilayer
Pfam= PF00025
InterPro= IPR006689
SMART= ARF
PROSITE = PDOC01020
SCOP = 1hur
TCDB =
OPM family= 99
OPM protein= 1ksg
PDB=PDB3|2al7A:18-181 PDB3|1zd9A:18-181 PDB3|1hurA:5-177PDB3|1u81A:17-177 PDB3|1o3yB:17-177 PDB3|1rrgA:5-177PDB3|1rrf :5-177 PDB3|1r8qA:5-177 PDB3|1s9dA:17-177PDB3|1r8sA:17-177 PDB3|1j2jA:18-177 PDB3|1z6xB:5-177PDB3|2b6hA:7-177 PDB3|1hfvA:1-173 PDB3|2a5fA:1-173PDB3|2a5dA:1-173 PDB3|1e0sA:1-173 PDB3|2a5gA:1-173PDB3|1uptC:15-177 PDB3|1r4aC:16-177 PDB3|1mozB:5-178PDB3|1zj6A:4-176 PDB3|1z6yB:4-176 PDB3|1yzgA:1-176PDB3|1ksjA:3-176 PDB3|1kshA:3-176 PDB3|1ksgA:3-176PDB3|1fzqA:3-177 PDB3|1m2oD:9-190 PDB3|1f6bB:11-197

ADP Ribosylation Factors (ARFs) are members of the ARF family of GTP-binding proteins of the Ras superfamily. ARF family proteins are ubiquitous in eukaryotic cells, and six highly conserved members of the family have been identified in mammalian cells. Although ARFs are soluble, they generally associate with membranes because of N-terminus myristoylation. They function as regulators of vesicular traffic and actin remodelling.

The small ADP ribosylation factor (Arf) GTP-binding proteins are major regulators of vesicle biogenesis in intracellular trafficcite journal |author=Cherfils J, Renault L, Pasqualato S |title=Arf, Arl, Arp and Sar proteins: a family of GTP-binding proteins with a structural device for 'front-back' communication |journal=EMBO Rep. |volume=3 |issue=11 |pages=1035–1041 |year=2002 |pmid=12429613 |doi=10.1093/embo-reports/kvf221] . They are the founding members of a growing family that includes Arl (Arf-like), Arp (Arf-related proteins) and the remotely related Sar (Secretion-associated and Ras-related) proteins. Arf proteins cycle between inactive GDP-bound and active GTP-bound forms that bind selectively to effectors. The classical structural GDP/GTP switch is characterised by conformational changes at the so-called switch 1 and switch 2 regions, which bind tightly to the gamma-phosphate of GTP but poorly or not at all to the GDP nucleotide. Structural studies of Arf1 and Arf6 have revealed that although these proteins feature the switch 1 and 2 conformational changes, they depart from other small GTP-binding proteins in that they use an additional, unique switch to propagate structural information from one side of the protein to the other.

The GDP/GTP structural cycles of human Arf1 and Arf6 feature a unique conformational change that affects the beta2beta3 strands connecting switch 1 and switch 2 (interswitch) and also the amphipathic helical N-terminus. In GDP-bound Arf1 and Arf6,the interswitch is retracted and forms a pocket to which the N-terminal helix binds, the latter serving as a molecular haspto maintain the inactive conformation. In the GTP-bound form of these proteins, the interswitch undergoes a two-residue register shift that pulls switch 1 and switch 2 up, restoring an active conformation that can bind GTP. In this conformation, the interswitch projects out of the protein and extrudes the N-terminal hasp by occluding its binding pocket.

Regulatory proteins

ARFs regularly associate with two types of protein, those involved in catalyzing GTP/GDP exchange, and those that serve other functions.

GTP/GDP exchange proteins

ARF binds to two forms of the guanosine nucleotide, guanosine triphosphate (GTP) and guanosine diphosphate (GDP). The shape of the ARF molecule is dependent upon which form it is bound to, allowing it to serve in a regulatory capacity. ARF requires assistance from other proteins in order to switch between binding to GTP and GDP. GTPase activating proteins (GAPs) force ARF to hydrolyze bound GTP to GDP, and Guanine nucleotide exchange factors force ARF to adopt a new GTP molecule in place of a bound GDP.

Other proteins

Other proteins interact with ARF dependent whether it is bound to GTP or GDP. The active form, ARF*GTP, binds to vesicle coat proteins and adaptors, including coat protein I COPI and various phospholipids. The inactive form is only know to bind to a class of transmembrane proteins.Different types of ARF bind specifically different kinds of effector proteins.

Phylogeny

There are currently 6 known mammalian ARF proteins, which are divided into three classes of ARFs:

* class 1: Gene|ARF1, Gene|ARF2, Gene|ARF3
* class 2: Gene|ARF4, Gene|ARF5
* class 3: Gene|ARF6. (See also ARF6)

tructure

ARFs are small proteins of approximately 20 kD in size. They contain two switch regions, which change relative positions between cycles of GDP/GTP-binding. ARFs are frequently myristoylated in their N-terminal region, which contributes to their membrane association.

Human proteins containing this domain

ARF1; ARF3; ARF4; ARF5; ARF6; ARFRP1; ARL1; ARL10;
ARL11; ARL13A; ARL13B; ARL14; ARL15; ARL16; ARL17; ARL2;
ARL2L1; ARL3; ARL4A; ARL4C; ARL4D; ARL5; ARL5A; ARL5B;
ARL6; ARL7; ARL8A; ARL8B; ARL9; MGC57346; SAR1A; SAR1B;
SAR1P3; SARA1; TRIM23;

References

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*

Further reading

* [1] . Structure of the human ADP-ribosylation factor 1 complexed with GDP. Amor JC, Harrison DH, Kahn RA, Ringe D; Nature 1994;372:704-708. PMID|7990966
* [2] . Structure and function of ARF proteins: Activators of cholera toxin and critical components of intracellular vesicular transport processes. Moss J, Vaughan M; J. Biol. Chem. 1995;270:12327-12330. PMID|7759471
* [3] . Arf proteins: the membrane traffic police? Boman AL, Kahn RA; Trends Biochem Sci 1995;20:147-150. PMID|7770914
* [4] . Human ADP-ribosylation factors. A functionally conserved family of GTP-binding proteins. Kahn RA, Kern FG, Clark J, Gelmann EP, Rulka C; J Biol Chem 1991;266:2606-2614. PMID|1899243


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