Structural Organization of FtsB, a Transmembrane Protein of the Bacterial Divisome

We
report the first structural analysis of an integral membrane
protein of the bacterial divisome. FtsB is a single-pass membrane
protein with a periplasmic coiled coil. Its heterologous association
with its partner FtsL represents an essential event for the recruitment
of the late components to the division site. Using a combination of
mutagenesis, computational modeling, and X-ray crystallography, we
determined that FtsB self-associates, and we investigated its structural
organization. We found that the transmembrane domain of FtsB homo-oligomerizes
through an evolutionarily conserved interaction interface where a
polar residue (Gln 16) plays a critical role through the formation
of an interhelical hydrogen bond. The crystal structure of the periplasmic
domain, solved as a fusion with Gp7, shows that 30 juxta-membrane
amino acids of FtsB form a canonical coiled coil. The presence of
conserved Gly residue in the linker region suggests that flexibility
between the transmembrane and coiled coil domains is functionally
important. We hypothesize that the transmembrane helices of FtsB form
a stable dimeric core for its association with FtsL into a higher-order
oligomer and that FtsL is required to stabilize the periplasmic domain
of FtsB, leading to the formation of a complex that is competent for
binding to FtsQ, and to their consequent recruitment to the divisome.
The study provides an experimentally validated structural model and
identifies point mutations that disrupt association, thereby establishing
important groundwork for the functional characterization of FtsB in vivo.