ยท H-J Yeo, S.E. Cotter, S. Laarmann, T.
Juehne, J.W. St. Geme, III, and G. Waksman
Structural basis for host recognition by the Haemophilus influenzae Hia autotransporter
EMBO Journal. 23:1245-56 (2004)
Haemophilus influenzae is an important human pathogen that
initiates infection by colonizing the upper respiratory tract. The H. influenzae Hia autotransporter is an adhesive
protein that promotes adherence to respiratory epithelial cells. Hia adhesive activity resides in two
homologous binding domains, called HiaBD1 and HiaBD2. These domains interact with the same host cell receptor, but
bind with different affinities. In
this report, we describe the crystal structure of the high-affinity HiaBD1
binding domain, which has a novel trimeric architecture with three-fold
symmetry and a mushroom shape. The
subunit constituents of the trimer are extensively intertwined. The receptor-binding pocket is formed
by an acidic patch that is present on all three faces of the trimer, providing
potential for a multivalent interaction with the host cell surface, analogous
to observations with the trimeric tumor necrosis factor superfamily of
proteins. Hia is a novel example
of a bacterial trimeric adhesin and may be the prototype member of a large
family of bacterial virulence proteins with a similar architecture.