ยท G. Meng, N.K. Surana, J. StGemes, and G.
Waksman
Structure of the outer membrane translocator domain of the Haemophilus
influenzae Hia trimeric
autotransporter
EMBO Journal. 25:2297-304 (2006)
Autotransporter proteins are defined by the ability to drive their
own secretion across the bacterial outer membrane. The Hia autotransporter of Haemophilus
influenzae belongs to the
trimeric autotransporter subfamily and mediates bacterial adhesion to the
respiratory epithelium. In this report we present the crystal structure of the
C-terminal end of Hia, corresponding to the entire Hia translocator domain and
part of the passenger domain (residues 992-1098). This domain forms a
beta-barrel with 12 transmembrane beta-strands, including four strands from
each subunit. The beta-barrel has a
central channel of 1.8nm in diameter that is traversed by three N-terminal
alpha-helices, one
from each subunit. Mutagenesis studies demonstrate that the transmembrane
portion of the three alpha-helices and the loop region between the alpha-helices and the neighboring beta-strands
are essential for stability of the trimeric structure of the translocator
domain and that trimerization of the translocator domain is a prerequisite for
translocator activity. Overall,
this study provides important insights into the mechanism of translocation in
trimeric autotransporters.