2xto
From Proteopedia
CRYSTAL STRUCTURE OF GDP-BOUND HUMAN GIMAP2, AMINO ACID RESIDUES 21-260
Structural highlights
Publication Abstract from PubMedGTPases of immunity-associated proteins (GIMAPs) are a distinctive family of GTPases, which control apoptosis in lymphocytes and play a central role in lymphocyte maturation and lymphocyte-associated diseases. To explore their function and mechanism, we determined crystal structures of a representative member, GIMAP2, in different nucleotide-loading and oligomerization states. Nucleotide-free and GDP-bound GIMAP2 were monomeric and revealed a guanine nucleotide-binding domain of the TRAFAC (translation factor associated) class with a unique amphipathic helix alpha7 packing against switch II. In the absence of alpha7 and the presence of GTP, GIMAP2 oligomerized via two distinct interfaces in the crystal. GTP-induced stabilization of switch I mediates dimerization across the nucleotide-binding site, which also involves the GIMAP specificity motif and the nucleotide base. Structural rearrangements in switch II appear to induce the release of alpha7 allowing oligomerization to proceed via a second interface. The unique architecture of the linear oligomer was confirmed by mutagenesis. Furthermore, we showed a function for the GIMAP2 oligomer at the surface of lipid droplets. Although earlier studies indicated that GIMAPs are related to the septins, the current structure also revealed a strikingly similar nucleotide coordination and dimerization mode as in the dynamin GTPase. Based on this, we reexamined the relationships of the septin- and dynamin-like GTPases and demonstrate that these are likely to have emerged from a common membrane-associated dimerizing ancestor. This ancestral property appears to be critical for the role of GIMAPs as nucleotide-regulated scaffolds on intracellular membranes. Structural basis of oligomerization in septin-like GTPase of immunity-associated protein 2 (GIMAP2).,Schwefel D, Frohlich C, Eichhorst J, Wiesner B, Behlke J, Aravind L, Daumke O Proc Natl Acad Sci U S A. 2010 Nov 8. PMID:21059949[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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