Figure 2. Modular model of lipoprotein secretion pathways in monoderm and diderm bacteria.

Lipoprotein secretion is mediated by a sequence of pathway modules. (1) The first module exports lipoprotein precursors through the cytoplasmic or inner membrane via the Sec or TAT pathways. (2) The second module processes the N-terminus of the proteins to yield a mature lipidated protein; in monoderm bacteria, the last modification step is dispensable, as indicated by a vertical dashed line. In diderm bacteria, IM lipoproteins like E. coli Nlp are retained by failure to interact with downstream pathways. (3) In diderm bacteria, OM lipoproteins can subsequently interact with three modules: (a) the Lol periplasmic sorting module uses the energy from ATP hydrolysis to release lipoproteins like E. coli Lpp from the IM, provides a carrier chaperone for transport through the periplasm and an OM membrane receptor for insertion into the inner leaflet of the OM. Lpp also assumes an integral membrane protein conformation leading to surface exposure of its C terminus. (b) The T2SS module uses assembly of a pseudopilus on a periplasmic platform to drive secretion of a specific surface lipoprotein such as K. oxytoca PulA through an OM pore. (c) The T5SS module involves the BAM complex in the OM and the integral membrane protein chaperones Skp, SurA and DegP as well to facilitate OM insertion and pore formation of NalP’s translocator domain (T) and subsequent translocation of its N-terminal passenger domain (P) through the OM. N. gonorrhoeae NalP is released from the cell by autolytic cleavage. (d) A proposed module mediates complete surface localization of spirochetal lipoproteins such as B. burgdorferi OspA by interaction with a holding chaperone and an outer membrane lipoprotein flippase complex. Any specific involvement of the Lol pathway remains to be resolved. See text for details.