2XTM

Crystal structure of GDP-bound human GIMAP2, amino acid residues 1- 234

Summary for 2XTM

• Entry DOI: 10.2210/pdb2xtm/pdb
• Related: 2XTN 2XTO 2XTP
• Descriptor: GTPASE IMAP FAMILY MEMBER 2, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: immune system, g protein
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Membrane; Multi-pass membrane protein (Potential): Q9UG22
• Total number of polymer chains: 2
• Total formula weight: 52985.59

Authors

Schwefel, D.,Froehlich, C.,Daumke, O. (deposition date: 2010-10-11, release date: 2010-10-20, Last modification date: 2024-05-08)

Primary citation

Schwefel, D.,Froehlich, C.,Eichhorst, J.,Wiesner, B.,Behlke, J.,Aravind, L.,Daumke, O.
Structural Basis of Oligomerization in Septin-Like Gtpase of Immunity-Associated Protein 2 (Gimap2)
Proc.Natl.Acad.Sci.USA, 107:20299-, 2010

PubMed Abstract: GTPases 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 α7 packing against switch II. In the absence of α7 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 α7 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.

PubMed: 21059949
DOI: 10.1073/PNAS.1010322107

Experimental method

X-RAY DIFFRACTION (1.7 Å)