F
IPR003578

Small GTPase Rho

InterPro entry
Short nameSmall_GTPase_Rho
Overlapping
homologous
superfamilies
 
family relationships

Description

This entry represents the Rho subfamily of Ras-like small GTPases. The small GTPase-like protein LIP2 (light insensitive period 2) fromArabidopsis thalianais implicated in control of the plant circadian rhythm
[9]
. The crystal structures of a number of the members of this entry have been determined: Rnd3/RhoE
[2]
, RhoA
[3]
and Cdc42
[1]
.

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
[4, 5]
. 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
[6]
.

Crystallographic analysis of various small G proteins revealed the presence of a 20kDa catalytic domain that is unique for the whole superfamily
[5, 7]
. 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 form, 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
[8]
.

The small GTPase superfamily can be divided into at least 8 different families, including:


 * Arf small GTPases. GTP-binding proteins involved in protein trafficking by modulating vesicle budding and uncoating within the Golgi apparatus.
 * Ran small GTPases. GTP-binding proteins involved in nucleocytoplasmic transport. Required for the import of proteins into the nucleus and also for RNA export.
 * Rab small GTPases. GTP-binding proteins involved in vesicular traffic.
 * Rho small GTPases. GTP-binding proteins that control cytoskeleton reorganisation.
 * Ras small GTPases. GTP-binding proteins involved in signalling pathways.
 * Sar1 small GTPases. Small GTPase component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).
 * Mitochondrial Rho (Miro). Small GTPase domain found in mitochondrial proteins involved in mitochondrial trafficking.
 * Roc small GTPases domain. Small GTPase domain always found associated with the COR domain.

References

1.Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP. Nassar N, Hoffman GR, Manor D, Clardy JC, Cerione RA. Nat. Struct. Biol. 5, 1047-52, (1998). View articlePMID: 9846874

2.Crystal structure of Rnd3/RhoE: functional implications. Fiegen D, Blumenstein L, Stege P, Vetter IR, Ahmadian MR. FEBS Lett. 525, 100-4, (2002). View articlePMID: 12163169

3.MgF(3)(-) as a transition state analog of phosphoryl transfer. Graham DL, Lowe PN, Grime GW, Marsh M, Rittinger K, Smerdon SJ, Gamblin SJ, Eccleston JF. Chem. Biol. 9, 375-81, (2002). View articlePMID: 11927263

4.The GTPase superfamily: a conserved switch for diverse cell functions. Bourne HR, Sanders DA, McCormick F. Nature 348, 125-32, (1990). View articlePMID: 2122258

5.The GTPase superfamily: conserved structure and molecular mechanism. Bourne HR, Sanders DA, McCormick F. Nature 349, 117-27, (1991). View articlePMID: 1898771

6.The ras protein family: evolutionary tree and role of conserved amino acids. Valencia A, Chardin P, Wittinghofer A, Sander C. Biochemistry 30, 4637-48, (1991). View articlePMID: 2029511

7.Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis. Pai EF, Krengel U, Petsko GA, Goody RS, Kabsch W, Wittinghofer A. EMBO J. 9, 2351-9, (1990). View articlePMID: 2196171

8.Structure of small G proteins and their regulators. Paduch M, Jelen F, Otlewski J. Acta Biochim. Pol. 48, 829-50, (2001). PMID: 11995995

9.Arabidopsis thaliana circadian clock is regulated by the small GTPase LIP1. Kevei E, Gyula P, Feher B, Toth R, Viczian A, Kircher S, Rea D, Dorjgotov D, Schafer E, Millar AJ, Kozma-Bognar L, Nagy F. Curr. Biol. 17, 1456-64, (2007). View articlePMID: 17683937

GO terms

molecular function

cellular component

  • None

Cross References

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