ADP ribosylation factor
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2008-05-28T19:28:56Z
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{{about|a small GTP-binding protein|p14ARF tumor suppressor gene|p14arf}}
{{Pfam_box
| Symbol = Arf
| Name =
| image = 1ksg_opm.gif
| 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|2al7}}A:18-181 {{PDB3|1zd9}}A:18-181 {{PDB3|1hur}}A:5-177
{{PDB3|1u81}}A:17-177 {{PDB3|1o3y}}B:17-177 {{PDB3|1rrg}}A:5-177
{{PDB3|1rrf}} :5-177 {{PDB3|1r8q}}A:5-177 {{PDB3|1s9d}}A:17-177
{{PDB3|1r8s}}A:17-177 {{PDB3|1j2j}}A:18-177 {{PDB3|1z6x}}B:5-177
{{PDB3|2b6h}}A:7-177 {{PDB3|1hfv}}A:1-173 {{PDB3|2a5f}}A:1-173
{{PDB3|2a5d}}A:1-173 {{PDB3|1e0s}}A:1-173 {{PDB3|2a5g}}A:1-173
{{PDB3|1upt}}C:15-177 {{PDB3|1r4a}}C:16-177 {{PDB3|1moz}}B:5-178
{{PDB3|1zj6}}A:4-176 {{PDB3|1z6y}}B:4-176 {{PDB3|1yzg}}A:1-176
{{PDB3|1ksj}}A:3-176 {{PDB3|1ksh}}A:3-176 {{PDB3|1ksg}}A:3-176
{{PDB3|1fzq}}A:3-177 {{PDB3|1m2o}}D:9-190 {{PDB3|1f6b}}B:11-197
}}
'''ADP Ribosylation Factors''' ('''ARFs''') are members of the ARF family of [[GTP-binding protein]]s 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 [[vesicle (biology)|vesicular]] traffic and [[actin]] remodelling.
The small ADP ribosylation factor (Arf) GTP-binding proteins are major regulators of vesicle biogenesis in intracellular traffic<ref name="PUB00009830">{{cite 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}}</ref>. 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 hasp
to 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|guanosine triphosphate]] (GTP) and [[Guanosine diphosphate|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 protein|GTPase activating proteins]] (GAPs) force ARF to [[hydrolysis|hydrolyze]] bound GTP to GDP, and [[Guanine nucleotide exchange factor|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|ARF6]])
==Structure==
ARFs are small proteins of approximately 20 [[kilodalton|kD]] in size. They contain two switch regions, which change relative positions between cycles of GDP/GTP-binding. ARFs are frequently [[Myristoylation|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==
{{reflist}}
* {{cite journal |author=Donaldson JG, Honda A |title=Localization and function of Arf family GTPases |journal=Biochem. Soc. Trans. |volume=33 |issue=Pt 4 |pages=639–42 |year=2005 |pmid=16042562 |doi=10.1042/BST0330639}}
* {{cite journal |author=Nie Z, Hirsch DS, Randazzo PA |title=Arf and its many interactors |journal=Curr. Opin. Cell Biol. |volume=15 |issue=4 |pages=396–404 |year=2003 |pmid=12892779 |doi=}}
==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}}
{{GTPases}}
{{InterPro content|IPR006689}}
[[Category:Protein domains]]
[[Category:Peripheral membrane proteins]]
[[de:Adenosyl-Ribosylierungs-Faktor]]