Small GTPases, also known as small G-proteins, are a large family of regulatory factors with roles in virtually all cellular processes. They essentially act as molecular switches, adopting either GDP-bound inactive (“off”) or GTP-bound active (“on”) states, through structural changes induced by the presence or absence of the γ-phosphate group of GTP.1 In humans, the small GTPase family contains approximately 150 members, and is further classified into five subfamilies—Ras, Rho, Arf, Rab, and Ran—based on their sequence and structure.2
The activity of these proteins is tightly regulated by a series of intricate mechanisms3 (Figure 1). Switching from the “off” to the “on” state is mediated by guanine nucleotide exchange factors (GEFs), which promote release of GDP and its replacement with GTP. Conversely, GTPase-activating proteins (GAPs) stimulate the normally slow intrinsic GTPase activity to enable rapid return to the “off” state. In this state, small GTPases are sometimes bound to guanine dissociation inhibitors (GDIs) to block interaction with GEFs and prevent activation. This elaborate control system is further enhanced by various protein–protein interactions and posttranslational modifications (PTMs),4 resulting in a highly complex regulatory network whose functioning has been the subject of intense research over the past few decades.
Given its importance, it is unsurprising to find that many pathogenic bacteria co-opt small GTPase signaling to invade and colonize host tissues. Here, we will illustrate just a few of the diverse strategies these pathogens use to subvert host cellular processes to their own advantage.
Also included in this newsletter
- Small G-Protein Tools
- Related Publications