Structural Basis for Oligomerization in the Septin‐like GTPase of Immunity‐Associated Proteins 2 (GIMAP2)

A novel vertebrate family of septin‐like GTP‐binding proteins termed GTPases of Immunity‐Associated Proteins (GIMAPs) is exclusively found in lymphocytes. Functional investigations of family members suggest a role in the regulation of apoptosis during lymphocyte development. The molecular mechanisms contributing to GIMAP function were studied in a biochemical and structural approach. GIMAP2 bound nucleotides with high affinity, dimerized in the presence of GTP and did not hydrolyze GTP. Crystal structures of several GIMAP2 constructs were solved in different nucleotide‐loading and oligomerization states. A function of GIMAP2 as nucleotide‐regulated scaffold for lipid droplet tethering and/or the assembly of interaction partners is suggested. While earlier studies indicated that GIMAPs are related to the septins, the current structure also revealed a strikingly similar dimerization mode as the dynamin GTPase. Based on this, we reexamined the relationships of the septin‐ and dynamin‐like GTPases and demonstrate that these have emerged from a common membrane‐associated dimerizing ancestor. The research was supported by the Max‐Delbrueck‐Centrum fuer Molekulare Medizin, Berlin, Germany.