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varied from their pilin counterparts required for their essential functions in host
adhesion and pilus assembly termination, respectively.
Adhesin
A mature CU pilus typically contains an adhesin at its distal end. Adhesins
contain two distinctive domains: a lectin domain, which functions to bind spe-
cific receptors with stereochemical specificity and contribute to host and tissue
tropisms, and an Ig-like pilin domain, which links the receptor-binding lectin
domain to the fibrillar tip ( Choudhury et al., 1999 ; Sauer et al., 1999 ). FimH
and PapG, adhesins of the prototypical type 1 and P pilus systems, respectively,
mediate host-pathogen interactions important in cystitis ( Wu et al., 1996 ;
Mulvey et al., 1998 ; Martinez et al., 2000 ; Bahrani-Mougeot et al., 2002 ) and
pyelonephritis ( Roberts et al., 1994 ). FimH mediates binding to α-D-mannose-
containing receptors whereas PapG binds galabiose, a receptor that is present
in the globo series glycolipids found in the kidney. Both lectin domains con-
tain a β-barrel jelly-roll fold that is common to CU adhesin structures, but they
contain different receptor-binding pockets. FimH contains a deep, negatively
charged pocket at the tip of the lectin domain ( Hung et al., 2002 ). In contrast,
PapGII (class II of three PapG classes, each of which recognize different globo
series of glycolipids) binds galabiose-containing receptors with a shallow bind-
ing pocket formed by three beta strands and a loop at the side of the lectin
domain ( Dodson et al., 2001 ). CU adhesins F17-G of ETEC ( Buts et al., 2003 )
and GafD of UPEC ( Merckel et al., 2003 ) bind N-acetyl-D-glucosamine resi-
dues of proteins at a shallow binding site on the side of the lectin domain at a
location unrelated to the binding pocket of PapG ( Figure 12.3 ). With the func-
tion of adhesion segregated to a distinct protein domain at the pilus tip, various
bacterial strains can alter the structure and receptor specificity of the adhesin,
thus allowing flexibility and selective advantage in establishing tropism.
Numerous studies suggest that the lectin domain of FimH does not operate
independently of the pilin domain but instead interacts intimately with it to
influence receptor binding. A crystal structure of the type 1 pilus tip fibrillum
( Le Trong et al., 2010 ) indicates a markedly different conformation in FimH,
compared to the conformation observed in FimH in the FimC-FimH complex
( Choudhury et al., 1999 ) or in the mannose-bound FimC-FimH structure ( Hung
et al., 2002 ). In the tip structure, the pilin domain interacts with a compacted
lectin domain in a stable, non-covalent manner, loosening the mannose-binding
pocket at the distal end of the lectin domain and thereby inducing an inac-
tive low-affinity state of the adhesin via a 'page-turning' allosteric mechanism
( Le Trong et al., 2010 ). In contrast, FimH, when in complex with FimC and
α-D-mannose, adopts an elongated, high-affinity state ( Hung et al., 2002 ),
which was later shown to be induced by application of shear force, presum-
ably by destabilization of interdomain contacts. Indeed, cross-linking mutants
along with positively selected residues in the pilin domain suggest that this
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