Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria

Tripartite efflux
pumps and the related type 1 secretion systems
(T1SSs) in Gram-negative organisms are diverse in function, energization,
and structural organization. They form continuous conduits spanning
both the inner and the outer membrane and are composed of three principal
componentsthe energized inner membrane transporters (belonging
to ABC, RND, and MFS families), the outer membrane factor channel-like
proteins, and linking the two, the periplasmic adaptor proteins (PAPs),
also known as the membrane fusion proteins (MFPs). In this review
we summarize the recent advances in understanding of structural biology,
function, and regulation of these systems, highlighting the previously
undescribed role of PAPs in providing a common architectural scaffold
across diverse families of transporters. Despite being built from
a limited number of basic structural domains, these complexes present
a staggering variety of architectures. While key insights have been
derived from the RND transporter systems, a closer inspection of the
operation and structural organization of different tripartite systems
reveals unexpected analogies between them, including those formed
around MFS- and ATP-driven transporters, suggesting that they operate
around basic common principles. Based on that we are proposing a new
integrated model of PAP-mediated communication within the conformational
cycling of tripartite systems, which could be expanded to other types
of assemblies.