Adhesive pili of the chaperone-usher family - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 356

with any protein partners. The stability of the chaperone depends on the forma-
tion of a buried salt bridge composed of D196, E83, and R116, which lies at
the interdomain region ( Hung et al., 1999 ). E83 is part of the aspartate, argi-
nine, glutamate, and serine (DRES) motif, which is highly conserved in the
chaperone superfamily ( Hung et al., 1996 ). Situated at the end of the E1-F1
loop, part of the DRES motif packs against the hinge region connecting the two
domains ( Holmgren and Branden, 1989 ; Hung et al., 1996 ), where the aspartate
and arginine side chains from the DRES motif point out into solution, seem-
ingly suitable for protein-protein interactions ( Figure 12.2 A). It is plausible that
interactions with other proteins (subunits or usher domains) could cause confor-
mational changes that would be transmitted to the interdomain region, possibly
disrupting the salt bridge and thus facilitating a reorientation of the domains and
causing allosteric conformational changes in the chaperone that play a role in
the assembly of the CU pilus.
SUBUNITS
Pilins
There are several major functional types of pilin that may comprise a CU pilus,
including adhesins, adaptors, tip fibrillar subunits, pilus rod subunits, and ter-
minators ( Figure 12.1 ). Pilins, or pilus subunits, share an outstanding degree
of sequence and structural homology with one another, necessary for preserv-
ing common mechanisms of subunit-subunit, chaperone-subunit, and usher-
chaperone-subunit interactions needed for maturation of a functional pilus.
As described, the incomplete nature of the pilin fold insures either chaperone
binding (by DSC) or Nte binding (by DSE) to pilus subunits for their stabil-
ity, proper folding, and ultimate incorporation into the growing pilus. Thus,
the Nte, chaperone G1 strand, and the incomplete Ig-like fold of pilin subunits,
particularly the P1-P5 pockets, serve as common recognition motifs in the CU
pathway for the use of pilins as building blocks in the construction of a pilus.
However, structural distinctions across homologous pilins permit their
unique positions and functions along the pilus chain. For example, differences
in Nte sequence and hydrophobic pocket characteristics dictate subunit order-
ing. DSE reactions performed by incubating all combinations of Nte peptides
(based on the five Nte-containing Pap subunits) with all chaperone-subunit
complexes showed a range of reactivities ( Rose et al., 2008 ; Verger et al., 2008 ).
Reactions that occurred most rapidly were consistently those between cognate
groove-Nte partners. In addition to chaperone-subunit and subunit-subunit
interactions, subunits also contain specific surfaces that drive chaperone-
subunit-usher interactions. Differences in subunit structure and residue side
chains dictate selective trafficking to certain periplasmic domains of the usher
(see Ushers: Domain function and selectivity). Thus, adhesin and terminator
subunits, which occupy opposite ends of the pilus, adopt structures much more