This entry represents a branch of the small GTPase superfamily that includes the ADP ribosylation factor Arf, Arl (Arf-like), and Arp\n(Arf-related proteins). Arf proteins are major regulators of vesicle biogenesis in intracellular traffic [[cite:PUB00009830]]. They 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.
\n\nThis entry also includes Signal recognition particle receptor subunit beta (SRbeta), which is closely related to Arf- and Ras-type GTPases by sequence. It contains a cysteine within the G1 GTPase consensus sequence where most Ras-type GTPases contain a glycine and members of the Arf family of GTPases contain an aspartic acid at this position. The identity of this amino acid appears to be crucial to the activity of Arf and Ras GTPases, which explains why SR beta doesn't have GTPase activity and differs functionally from both Arf-like and other Ras-type GTPases [[cite:PUB00036002], [cite:PUB00117369]]. SRbeta is involved in the targeting of nascent polypeptide chains to the protein translocation machinery in the endoplasmic reticulum membrane.
","llm":false,"checked":false,"updated":false},{"text":"Small GTPases form an independent superfamily within the larger class of regulatory GTP hydrolases. This superfamily contains proteins that control a vast number of important processes and possess a common, structurally preserved GTP-binding domain [[cite:PUB00052600], [cite:PUB00004087]]. Sequence comparisons of small G proteins from various species have revealed that they are conserved in primary structures at the level of 30-55% similarity [[cite:PUB00000348]].
\n\nCrystallographic analysis of various small G proteins revealed the presence of a 20kDa catalytic domain that is unique for the whole superfamily [[cite:PUB00004087], [cite:PUB00023196]]. The domain is built of five α helices (A1-A5), six β-strands (B1-B6) and five polypeptide loops (G1-G5). A structural comparison of the GTP- and GDP-bound forms allows one to distinguish two functional loop regions: switch I and switch II that surround the gamma-phosphate group of the nucleotide. The G1 loop (also called the P-loop) that connects the B1 strand and the A1 helix is responsible for the binding of the phosphate groups. The G3 loop provides residues for Mg2 and phosphate binding and is located at the N terminus of the A2 helix. The G1 and G3 loops are sequentially similar to Walker A and Walker B boxes that are found in other nucleotide binding motifs. The G2 loop connects the A1 helix and the B2 strand and contains a conserved Thr residue responsible for Mg2 binding. The guanine base is recognised by the G4 and G5 loops. The consensus sequence NKXD of the G4 loop contains Lys and Asp residues directly interacting with the nucleotide. Part of the G5 loop located between B6 and A5 acts as a recognition site for the guanine base [[cite:PUB00015117]].
\n\nThe small GTPase superfamily can be divided into at least 8 different families, including:
\n\n