ADP ribosylation factor

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

	Membrane-bound ADP ribosylation factor-like protein 2 (ARL2 mouse, red), complex with phosphodiesterase delta (yellow) ( 1ksg ) Blue dots show hydrocarbon boundary of the lipid bilayer
Identifiers
Symbol	Arf
Pfam	PF00025
InterPro	IPR006689
SMART	ARF
PROSITE	PDOC01020
SCOP2	1hur / SCOPe / SUPFAM
OPM superfamily	124
OPM protein	1ksg
CDD	cd00878
Membranome	1103
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Last updated July 29, 2024

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 traffic.^[1] 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. ARFs act as a regulatory subunit that control coat assembly in coat protein I (COPI), and clathrin-coated vesicles.^{[ citation needed ]}

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 the form to which it is bound, 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, depending upon whether or not 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 known 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: ARF1 , ARF2 , ARF3
class 2: ARF4 , ARF5
class 3: ARF6 . (See also ARF6)

Structure

ARFs are small proteins of approximately 20 kDa 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.

Examples

Human genes encoding proteins containing this domain include:

Related Research Articles

GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a protein domain common to many GTPases.

Small GTPases, also known as small G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form guanosine diphosphate (GDP). The best-known members are the Ras GTPases and hence they are sometimes called Ras subfamily GTPases.

Guanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of a pyrophosphate group, a pentose sugar ribose, and the nucleobase guanine.

<span class="mw-page-title-main">Transducin</span>

Transducin (G_t) is a protein naturally expressed in vertebrate retina rods and cones and it is very important in vertebrate phototransduction. It is a type of heterotrimeric G-protein with different α subunits in rod and cone photoreceptors.

COPI is a coatomer, a protein complex that coats vesicles transporting proteins from the cis end of the Golgi complex back to the rough endoplasmic reticulum (ER), where they were originally synthesized, and between Golgi compartments. This type of transport is retrograde transport, in contrast to the anterograde transport associated with the COPII protein. The name "COPI" refers to the specific coat protein complex that initiates the budding process on the cis-Golgi membrane. The coat consists of large protein subcomplexes that are made of seven different protein subunits, namely α, β, β', γ, δ, ε and ζ.

ADP-ribosylation factor 6 (ARF6) is a member of the ADP ribosylation factor family of GTP-binding proteins. ARF6 has a variety of cellular functions that are frequently involved in trafficking of biological membranes and transmembrane protein cargo. ARF6 has specifically been implicated in endocytosis of plasma membrane proteins and also, to a lesser extent, plasma membrane protein recycling.

<span class="mw-page-title-main">Nucleotide exchange factor</span>

Nucleotide exchange factors (NEFs) are proteins that stimulate the exchange (replacement) of nucleoside diphosphates for nucleoside triphosphates bound to other proteins.

The coatomer is a protein complex that coats membrane-bound transport vesicles. Two types of coatomers are known:

<span class="mw-page-title-main">Guanine nucleotide exchange factor</span> Proteins which remove GDP from GTPases

Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity. Some GEFs can activate multiple GTPases while others are specific to a single GTPase.

ADP-ribosylation factor 1 is a protein that in humans is encoded by the ARF1 gene.

ADP-ribosylation factor-binding protein GGA1 is a protein that in humans is encoded by the GGA1 gene.

ADP-ribosylation factor 3 is a protein that in humans is encoded by the ARF3 gene.

ADP-ribosylation factor GTPase-activating protein 1 is an enzyme that in humans is encoded by the ARFGAP1 gene. Two transcript variants encoding different isoforms have been found for this gene.

ADP-ribosylation factor 5 is a protein that in humans is encoded by the ARF5 gene.

ADP-ribosylation factor-like protein 4A is a protein that in humans is encoded by the ARL4A gene.

ADP-ribosylation factor 4 is a protein that in humans is encoded by the ARF4 gene.

ADP-ribosylation factor-like protein 3 is a protein that in humans is encoded by the ARL3 gene.

ADP-ribosylation factor-like protein 6 is a protein that in humans is encoded by the ARL6 gene.

GTP-binding protein ARD-1 is a protein that in humans is encoded by the TRIM23 gene.

IQ motif and SEC7 domain-containing protein 1 also known as ARF-GEP₁₀₀ (ADP-Ribosylation Factor - Guanine nucleotide-Exchange Protein - 100-kDa) is a protein that in humans is encoded by the IQSEC1 gene.

References

↑ Pasqualato S, Renault L, Cherfils J (2002). "Arf, Arl, Arp and Sar proteins: A family of GTP-binding proteins with a structural device for 'front-back' communication". EMBO Reports. 3 (11): 1035–1041. doi:10.1093/embo-reports/kvf221. PMC 1307594 . PMID 12429613.

External links

Eukaryotic Linear Motif resource motif class TRG_Cilium_Arf4_1

This article incorporates text from the public domain Pfam and InterPro: IPR006689

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[PUB00009830-1] Pasqualato S, Renault L, Cherfils J (2002). "Arf, Arl, Arp and Sar proteins: A family of GTP-binding proteins with a structural device for 'front-back' communication". EMBO Reports. 3 (11): 1035–1041. doi:10.1093/embo-reports/kvf221. PMC 1307594 . PMID 12429613.

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