G-domain

Alone, P. V., and Dever, T. E. (2006). Direct binding of translation initiation factor eIF2gamma-G domain to its GTPase-activating and GDP—GTP exchange factors eIF5 and eIF2B epsilon. J. Biol. Client. 281, 12636—12644. 

Fig. 5.12. Structure of the G-domain of the elongation factor EF-Tu from T. ther-mophilus with bonnd GppNHp, according to Berchthold et al., (1993). The non-hydrolysable analog GppNHp, the P loop and the switch regions I and II are shown, which play an important role in transition from the inactive GDP form to the active GTP form (see also 5.5.6 and 9.2.1). MOLSKRIPT representation according to Kranhs, (1991).

Gt,a is made up of two domains, a GTPase domain and a helical domain. The GTPase or G-domain indicates that Gt, is a member of the superfamily of regulatory GTPases. In addition, G, possesses a helical domain, which represents a characteristic feature of the heterotrimeric G-proteins. The nucleotide binding site is in a cleft between the two domains. It is assumed that the presence of the helical domain is the reason that bound nucleotide dissociates only very slowly from transducin and that the activated receptor is therefore necessary to initiate the GDP/GTP exchange. 

The Ras protein, as a regulatory GTPase, shows the G domain typical for the superfamily of regulatory GTPases (see Fig. 5.12). The sequence motives characteristic for regulatory GTPases (c 5.3.3) are involved in binding the nucleotide and Mg. Three... 

The GTPase of the a-subimits of heterotrimeric G-proteins also uses an Arg residue (Argl78 in Fig. 5.18a,b) for stabilization of the transition state of hydrolysis. In contrast to the Ras protein, this is localized in the cis configuration on the a-subunit itself and is foimd in the linker between the helical domain and the G-domain. 

G proteins have a common core structure, the G domain of Mr about 21 000, that is virtually superimposable in all crystal structures so far solved.66-74... 

Hoffman MP, Nomizu M, Roque E et al. Laminin-1 and laminin-2 G-domain synthetic peptides bind syndecan-1 and are involved in acinar formation of a human submandibular gland cell line. J Biol Chem 1998 273 28633. 

The structure of a TRAF-C domain was first revealed from the crystal structure of the TRAP domain of human TRAF2 (Fig. 2A, E), alone and in complex with a receptor peptide from TNF-R2 (Park et al, 1999). The main structural architecture of the TRAF-G domain comprises an eight-stranded anti-parallel /3-sandwich, with strands j3, f38, (35, and (36 in one sheet and (32, (3S, (34, and (31 in the other. Visual inspection of the SCOP structure database (Murzin et al, 1995) and an automatic structural similarity search with the Dali program (Holm and Sander, 1995) showed that the TRAF-G domain represent a novel fold for an eight-stranded anti-parallel /3-sandwich. However, the topology observed... 

Sequence analysis showed that a diverse set of proteins with unrelated functions to TRAFs appear to contain the TRAF-G domain. These include meprins, a family of extracellular metalloproteases (Uren and Vaux, 1996), MUL, the product of the causative gene in Mulibrey Nanism syndrome, USP7 (HAUSP), an ubiquitin protease, and SPOP, a POZ (poxvirus and zinc finger) domain-containing protein (Zapata et al, 2001). Because of its similarities with meprins, TRAF-G domain was also dubbed meprin- and TRAF-homology (MATH) domain (Uren and Vaux, 1996). 

A most striking structural feature of the TRAF domain, comprising a coiled coil TRAF-N domain followed by the TRAF-G domain, is the formation of a mushroom-shaped trimer with the TRAF-G domain as the cap and the coUed-coU domain as the stalk (McWhirter et at, 1999 Park et al, 1999 Ye et al, 1999) (Fig. 3A, B). The trimer obeys perfect or near perfect threefold symmetry. The diameter of the mushroom cap ranges between 50 to 80 A while the stalk is approximately 50 A long for 5 heptad repeats (residues 311-347). 

Both the coiled coil domain and the TRAF-G domain mediate TRAF domain trimerization. The three-stranded parallel coiled coil structure is stabilized by hydrophobic residues at positions A and D of the... 

There are more than a hundred proteins in the ras super family. Each subfamily shares the common core G domain, which provides essential GTPase and nucleotide exchange activity. 

The zinc-ribbon motif is found in a diverse group of proteins with limited sequence similarity and includes proteins involved in transcription (e.g. Transcription Factor IIB" ) and translation (the G domain of the y-subunit of the heterotrimeric translation initiation factor In TFIIB, the surface... 

Ras proteins are composed of two discrete sequence elements a catalytic G domain and a hypervariable membrane-targeting... 

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