Exploring potassium-dependent GTP hydrolysis in TEES family GTPases

GTPases are important regulatory proteins that hydrolyze GTP to GDP. A novel GTP-hydrolysis mechanism is employed by MnmE, YqeH and FeoB, where a potassium ion plays a role analogous to the Arginine finger of the Ras-RasGAP system, to accelerate otherwise slow GTP hydrolysis rates. In these proteins, two conserved asparagines and a ‘K-loop’ present in switch-I, were suggested as attributes of GTPases employing a K+-mediated mechanism. Based on their conservation, a similar mechanism was suggested for TEES family GTPases. Recently, in Dynamin, Fzo1 and RbgA, which also conserve these attributes, a similar mechanism was shown to be operative. Here, we probe K+-activated GTP hydrolysis in TEES (TrmE-Era-EngA-YihA-Septin) GTPases – Era, EngB and the two contiguous G-domains, GD1 and GD2 of YphC (EngA homologue) – and also in HflX, another GTPase that also conserves the same attributes. While GD1-YphC and Era exhibit a K+-mediated activation of GTP hydrolysis, surprisingly GD2-YphC, EngB and HflX do not. Therefore, the attributes identified thus far, do not necessarily predict a K+-mechanism in GTPases and hence warrant extensive structural investigations.

▸ An emerging alternative mechanism of GTP hydrolysis is mediated by K+ ions. ▸ Features characteristic of the K+-mediated mechanism were suggested. ▸ As TEES family GTPases possess these, they were suggested to employ this mechanism. ▸ Not all GTPases that possess these features utilize the K+-mediated mechanism. ▸ Unambiguously identifying determinants of K+ mechanism requires extensive studies.