Discovery of new Longin and Roadblock domains that form platforms for small GTPases in Ragulator and TRAPP-II

Abstract

Guanine nucleotide exchange factors (GEFs) control the site and extent of GTPase activity. Longin domains (LDs) are found in many Rab-GEFs, including DENNs, MON1/CCZ1, BLOC-3 and the TRAPP complex. Other GEFs, including Ragulator, contain roadblock domains (RDs), the structure of which is closely related to LDs. Other GTPase regulators, including mglB, SRX and Rags, use LDs or RDs as platforms for GTPases. Here, we review the conserved relationship between GTPases and LD/RDs, showing how LD/RD dimers act as adaptable platforms for GTPases. To extend our knowledge of GEFs, we used a highly sensitive sequence alignment tool to predict the existence of new LD/RDs. We discovered two yeast Ragulator subunits, and also a new LD in TRAPPC10 that may explain the Rab11-GEF activity ascribed to TRAPP-II.