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seminars in C E L L & D E V E L OP M E N T A L B I OL OG Y, Vol 11, 2000: pp. 27᎐34
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PapD-like chaperones and pilus biogenesis
Frederic G. Sauer a, Stefan D. Knight c, Gabriel Waksman b and
Scott J. Hultgrena,U
tion, and assembly.1 The PapD-like superfamily of
periplasmic chaperones directs the assembly of an
array of adhesive surface organelles that mediate
attachment to host tissues, a critical early step in the
development of disease,1,2 ŽTable 1.. The elucidation
of the function of PapD-like chaperones has revealed
molecular details of a mechanism that has contributed to our understanding both of general principles of organelle development and of the pathogenesis of a variety of bacterial diseases.
The more than 30 known PapD-like chaperones
facilitate the assembly of both pilus and non-pilus
organelles2 ŽTable 1.. Much of our knowledge of the
function of these molecules comes from the study of
PapD and FimC, which assemble P and type 1 pili,
respectively, in E. coli 3 ᎐ 5 ŽFigure 1.. Genes important
in P Ž papA᎐papK . and type 1 Ž fimA᎐fimH . pilus
biogenesis are organized in the pap and fim operons,
respectively.1 P pili consist of six structural proteins
that interact to form a composite fiber with two
subassemblies: a 7-nm-thick pilus rod comprised of
PapA subunits arranged in a right-handed helical
cylinder, and a thin fibrillum comprised primarily of
PapE subunits arranged in an open helical configuration.6,7 The PapK adaptor protein links the two
subassemblies.8 The PapG adhesin, a virulence factor
in uropathogenic E. coli, is joined to the distal end of
the tip fibrillum by the PapF adaptor protein.8 ᎐ 10
Type 1 pili are also composite fibers consisting of a
short tip fibrillum containing the FimH adhesin,
joined to the distal end of a pilus rod.11
During pilus biogenesis, the chaperone interacts
with each nascently translocated pilus subunit in the
periplasm ŽFigure 1. via a mechanism termed donor
strand complementation Žsee below.. This interaction
facilitates the release of the subunit from the cytoplasmic membrane in a process that my be driven by
its folding directly on the chaperone template. The
chaperone remains bound to the folded subunit,
stabilizing it and capping its interactive surfaces and
The assembly of adhesive pili from individual subunits by
periplasmic PapD-like chaperones in Gram-negative bacteria
offers insight into the complex process of organelle biogenesis.
PapD-like chaperones bind, stabilize, and cap interactive
surfaces of subunits until they are assembled into the pilus.
Subunits lack the seventh ␤-strand necessary to complete
their immunoglobulin-like folds; the chaperone supplies this
missing strand. Indeed, the chaperone may act as a template,
providing steric information to facilitate subunit folding. In
the mature pilus, each subunit is thought to supply the
missing strand to complete the fold of its neighbor. Thus,
one general function of chaperones in organelle biogenesis
may be to cap highly interactive surfaces of subunits until
they reach the proper assembly site.
Key words: chaperone r pilus r organelle biogenesis r
protein folding
䊚2000 Academic Press
Introduction
A FUNDAMENTAL QUESTION in molecular biology is
how proteins fold into domains that can serve as
assembly modules for building up larger macromolecular structures. The biogenesis of large fibrous
organelles, called pili, on the surface of Gram-negative bacteria requires the orchestration of a complex
process that includes protein synthesis, folding, secre-
From the aDepartments of Molecular Microbiology, bBiochemistry
and Molecular Biophysics, Washington University School of
Medicine, St. Louis, MO 63110, USA, and cDepartment of
Molecular Biology, Uppsala Biomedical Center, Swedish University
U
of Agricultural Sciences, Uppsala, Sweden. Corresponding author.
䊚2000 Academic Press
1084-9521r 00 r 010027q 08 $35.00r 0
27
F. G. Sauer et al.
Table 1. Bacterial surface organelles assembled by PapD-like chaperones
Organelle Žreference.
Fibers
P pilus
Prs pilus
Type 1 pilus
Organism
Chaperone
PapC
PrsC
FimD
Pyelonephritis, cystitis
Cystitis?
Cystitis
FocC
SfaE
HifB
HafB
FocD
SfaF
HifC
HafC
Cystits?
UTI, NBM
Otitis media, meningitis
Brazilian purpuric fever
FimB ŽFhaD.
PefD
LpfB
MrpD
PmfD
AftB
AfrC
FanE
FimC ŽFhaA.
PefC
LpfC
MrpC
PmfC
AftC
AfrB
FanD
E. coli
E. coli
ETEC
K. pneumoniae
FaeE
FasB
F17D
MrkB
FaeD
FasD
F17papC
MrkC
Whopping cough
Gastroenteritis, samonellosis
Gastroenteritis?, samonellosis?
Nosocomial UTI
Nosocomial UTI
UTI
Diarrhea in rabbits
Neonatal diarrhea in calves,
lambs, piglets
Neonatal diarrhea in piglets
Diarrhea in piglets
Diarrhea in piglets
Pneumonia
E. coli
E. coli
E. coli
E. coli
NfaE
AfaB
DraE
BmaB
NfaC
AfaC
DraD
BmaC
UTI, NBM
Pyelonephritis
UTI, diarrhea
Pyelonephritis
ETEC
ETEC
ETEC
ETEC
S. enteritidis
Yersinia pestis
Y. pestis,
Y. pseudotuberculosis
Y. enteritidis
Cs3-1
ClpE
CssC
AggD
SefB
Caf1M
PsaB
Cs3-2
ClpD
CssD?
AggC
SefC
Caf1A
PsaC
Traveler’s diarrhea
Diarrhea
Diarrhea
Diarrhea
Gastroenteritis, salmonellosis
Plague
Plague
MyfB
MyfC
Entercolitis
RalE
RalD
Diarrhea in rabbits
Type 2 and 3 pili
Pef pilus
Lpf pilus
MRrP pilus
PMF pilus
Aft pilus
AFrR1 pilus38
K99 pilus
K88 pilus
987P pilus
F17 pilus
MRrK ŽType 3. pilus
Non-fimbrial Adhesins
NFA1-6 family
Afa-1
DrrAfa-111
M
Atypical structures
CS3
CS31A pilus
CS6 pilus
AAFr1
Sef
F1 antigen
PH6 antigen
Myf
Unknown structures
?
Disease
PapD
PrsD
FimC
E. coli
E. coli
E. coli, Salmonella ssp.,
Klebsiella pneumoniae
E. coli
E. coli
Hemophilus influenzae
H. influenzae biogroup
aegyptius
Bordetella pertussis
S. typhimurium
S. typhimurium
Proteus mirabilis
P. mirabilis
P. mirabilis
E. coli
E. coli
F1C pilus
S pilus
Hif pilus
Haf pilus
Usher
REPEC
17
Notes. Adapted from Table 1 in Thanassi et al. See refs 2 and 17 for references not listed. UTI, urinary tract infection;
NBM, newborn meningitis; ETEC, enterotoxigenic E. coli; REPEC, rabbit enteropathogenic E. coli.
thus preventing premature aggregation in the
periplasm.12 ᎐ 16 Each PapD-like chaperone functions
in concert with a corresponding outer membrane
usher protein.17 Chaperone᎐subunit complexes are
specifically targeted to the usher, which forms a 2᎐3nm diameter donut-shaped channel, large enough to
allow the passage of pilus subunits.18,19 In the fim and
pap systems, it has been shown that the chaperone᎐
adhesin complex binds most rapidly and tightly to
the usher in a process that is thought to initiate pilus
assembly. Formation of a chaperone᎐adhesin᎐usher
ternary complex induces a conformational change in
the usher to an assembly-competent form that is
maintained throughout pilus assembly.20 The usher
facilitates chaperone uncapping to expose the interactive surfaces on the subunits that drive their assembly into the pilus. The pilus is thought to grow
through the usher as a linear fiber that packages into
its final quaternary structure upon reaching the bacterial surface.19
28
Chaperones and pilus biogenesis
Figure 1. Schematic of P pilus biogenesis. P pili are members of a large family of surface
organelles assembled by PapD-like chaperones and their corresponding ushers. Electron micrographs of a P pilus and a type 1 pilus from E. coli are shown Ž1.. Pilus subunits enter the
periplasm through the Sec transport system. In the absence of the PapD periplasmic chaperone,
subunits aggregate and are degraded Ž2., inducing signal transduction in the bacterium. In the
presence of PapD, subunits form stable chaperone᎐subunit complexes Ž3. through a mechanism
termed donor strand complementation Žthe PapD᎐PapK chaperone᎐subunit complex is shown.
Ž4., in which the chaperone donates its G1 ␤-strand to complete the Ig fold of the subunit ŽFigure
2.. This interaction permits subunit folding and prevents both subunit aggregation and premature subunit polymerization. The chaperone᎐subunit complexes are then targeted to an outer
membrane protein pore termed the usher ŽPapC., where the subunits assemble into a pilus. The
chaperone᎐adhesin complex ŽPapD᎐PapG. binds most rapidly and tightly to the usher, initiating
pilus assembly Ž5.. Assembly of subsequent subunits Ž6. occurs through a mechanism termed
donor strand exchange Ž7., in which the disordered N-terminus of an incoming subunit displaces
the G1 strand of the chaperone in the most recently assembled chaperone᎐subunit complex
ŽFigure 3.. Thus, in the mature pilus, the Ig fold of a subunit is completed by the N-terminal
strand of the adjacent subunit. The rod subunits ŽPapA. wind into their final helical form once
outside the cell Ž8., a process that is thought to facilitate the outward growth of the pilus. An
electron micrograph of an unwound pilus rod is shown Ž9..
known as the Cpx pathway.12,21 The Cpx pathway
responds to periplasmic stress by inducing the activation of a variety of genes encoding periplasmic protein folding factors ŽDsbA and prolyl isomerases. and
periplasmic proteases ŽDegP..21 ᎐ 23 DegP degrades
misfolded pilins, preventing their toxic buildup in
The Cpx pathway
In the absence of the chaperone, subunits are unstable and misfold, aggregate, and are proteolytically
degraded. OFF-pathway subunits have been shown to
activate a two-component signal transduction system
29
F. G. Sauer et al.
the periplasm. DsbA catalyzes disulfide bond formation in proteins required for the assembly of P pili.24
Thus, Cpx is part of a pilus biogenesis sensorrcontrol
circuit ŽFigure 1. that ensures that toxic OFF-pathway
products do not accumulate.12
Chaperone–subunit complexes: donor strand
complementation
The crystal structure of PapD and the solution structure of FimC, and more recently, the crystal structures of the FimC᎐FimH chaperone᎐adhesin complex and the PapD᎐PapK chaperone᎐pilin complex
have all been solved.25 ᎐ 28 The chaperone consists of
two immunoglobulin-like ŽIg. domains oriented in an
L-shape to form a cleft between them. The apo and
complexed forms of the chaperone are virtually superimposable, with the exception of the F1 ᎐G1 loop,
as discussed below. The FimH adhesin consists of two
domains: a pilin domain and a receptor-binding domain. The PapK pilin and the pilin domain of FimH
have Ig folds; however, they lack the seventh and
C-terminal ␤-strand Žstrand G. present in canonical
Ig folds ŽFigure 2.. The absence of this strand produces a deep groove along the surface of the pilin
domain and exposes its hydrophobic coreᎏhence
the instability of pilins when expressed without the
chaperone. In the chaperone᎐subunit complex, the
G1 strand of the chaperone and a portion of the
F1 ᎐G1 loop, which extends to lengthen the G1 strand,
complete the Ig fold of the subunit by occupying the
groove. This donor strand complementation interaction stabilizes the subunit by shielding its hydrophobic core. Indeed, alternating hydrophobic
residues in the G1 strand become an integral part of
the hydrophobic core of the subunit. The G1 strand
provides the missing strand of the subunit Ig domain
by interacting with strands A2 Žalso called A⬙ . and F
located on either side of the groove, while the Cterminal carboxyl group of the subunit, at the end of
the F strand, is anchored between the conserved Arg
and Lys residues29 in the cleft of the chaperone
ŽFigure 2.. The Ig fold that is produced is atypical
since the G1 strand of the chaperone runs parallel,
rather than anti-parallel, to the F strand, as it does in
a canonical Ig fold.27,28,30 While stabilizing the subunit and completing its fold, the chaperone simultaneously caps one of its interactive surfaces. Mutational and biochemical studies indicate that the groove
of the pilus subunit that participates in donor strand
complementation is the same surface that interacts
Figure 2. Donor strand complementation interactions in
the FimC᎐FimH chaperone᎐adhesin complex. FimC is
shown in black and FimH is in gray. The G1 ␤-strand
completes the Ig fold of the FimH pilin domain between
the A⬙ Ži.e. A2. and F strands. The G1 ␤-strand runs
parallel to the F strand. The alternating hydrophobic
residues of the G1 ␤-strand ŽLeu103, Leu105, Ile107 in
FimC. form part of the hydrophobic core of the pilin
domain and may facilitate the collapse of the hydrophobic
core during subunit folding. The C-terminal carboxyl group
ŽCOOH. is anchored in the cleft between the two domains
of FimC by the conserved Arg8 and Lys112 residues.
with other subunits in the pilus.14,16 Thus, the G1
strand of the chaperone, by occupying the groove,
prevents premature pilus formation in the periplasm.
Donor strand exchange and pilus biogenesis
Pilus subunits have an N-terminal extension Žresidues
1᎐13 in PapK, for example. with a highly conserved
alternating hydrophobic motif that has been shown
to participate in subunit᎐subunit interactions.16 This
motif is similar to the alternating hydrophobic motif
present in the G1 ␤-strand of the chaperone that
participates in donor strand complementation. The
N-terminal extension does not contribute to the Ig
fold of the subunit, but rather projects away from the
rest of the pilin domain where it would be free to
interact with another subunit.28 Based on these
observations, we propose that during pilus biogenesis, the N-terminal extension of one subunit displaces
the chaperone G1 strand from its neighboring subunit in a mechanism termed donor strand
exchange27,28 ŽFigure 3.. The pilin domain of the
adhesin lacks this N-terminal extension, consistent
30
Chaperones and pilus biogenesis
one prevents non-productive interactions, thereby
keeping it ON pathway. However, the PapD-like
chaperones may play a more active role by providing
a structural context for subunit folding. Donor strand
complementation might occur either early or late in
the folding pathway, but once the subunit is folded,
the chaperone remains bound, capping the critical
subunit groove. In other words, the chaperone may
couple the folding of the subunit with the capping of
the groove. Then, during donor strand exchange, the
N-terminal extension of the neighboring subunit
would replace the G1 strand of the chaperone in the
groove, thus preventing the exposure of the interactive groove at any time during the entire folding and
assembly pathway.
␤-sheet formation is thought to be determined in a
large part by tertiary context, even at solvent-accessible sites, and not by intrinsic secondary structural
preferences.31 Donation of the G1 strand of the chaperone may provide the necessary tertiary context for
the formation of the G1 , F, C1 ␤-sheet,16 which forms
half of the immunoglobulin fold of the pilin
domain.27,28 Indeed, PapD is known to induce the
formation of ␤-strands in peptides corresponding to
the C-terminal F strands of subunits.15,16,32 During
chaperone᎐subunit complex formation, the interaction between the C-terminal carboxyl group at the
end of the subunit F strand and the conserved Arg
and Lys residues in the chaperone cleft would position the F strand correctly in relation to the chaperone G1 strand during subunit folding ŽFigure 2.. At
the same time, this interaction would position the
hydrophobic side chains of strand F to allow them to
make the appropriate contacts with the alternating
hydrophobic residues in the chaperone G1 strand.
Thus, by providing the correct context for beta sheet
formation, the G1 strand of the chaperone may facilitate the proper collapse of the hydrophobic core of
the subunit ŽFigure 2..
Figure 3. Proposed model of subunit᎐subunit interactions
in a pilus. The N-terminal extension of one subunit replaces the chaperone G1 strand and completes the Ig fold
of the preceding subunit, running anti-parallel to the F
strand.
with its location at the tip of the pilus.27 The subsequent order of subunits in the pilus may at least in
part be determined by the stereochemical complementarity between the N-terminal extension of the
subunit and the groove of its neighbor.27,28 The
known geometry of pilus rods indicates that the Nterminal strand would insert anti-parallel to the F
strand of the neighboring subunit, unlike the chaperone G1 strand, which inserts in a parallel fashion.27,28
The mature pilus would thus consist of an array of
perfectly canonical Ig domains, each of which contributes a strand to the fold of the preceding subunit
to produce the organelle.
Protein folding with a novel twist
Donor strand complementation simultaneously
stabilizes the pilus subunit and caps the interactive
groove. In addition, donor strand complementation
permits subunit folding. In the absence of the chaperone, subunits aggregate in the periplasm and are
degraded by the DegP protease.12 These non-productive interactions are thought to interfere with the
proper folding pathway. For example, PapG expressed in the absence of the chaperone in a degPy
strain does not fold into a native receptor binding
conformation.12 Therefore, by providing the seventh
G strand to complete the subunit Ig fold, the chaper-
Cytoplasmic and periplasmic chaperones
The PapD-like chaperones differ in several respects
from the DnaJrDnaKrGrpE and GroELrGroES cytoplasmic chaperone systems reviewed in this issue
Žsee preceding paper by Agashe and Hartl. as well as
in ref 33. DnaJ and DnaK bind to semiunfolded polypeptides and maintain them in
folding-competent conformations by preventing them
from engaging in non-productive interactions. DnaJ
31
F. G. Sauer et al.
A model for organelle biogenesis?
is thought to be released from the ternary complex,
leaving DnaK tightly bound to the polypeptide. GrpE
is then thought to facilitate the release of the
polypeptide from DnaK, allowing it to fold in solution. In the GroELrGroES system, semi-unfolded or
misfolded polypeptides interact with the hydrophobic
walls of the GroEL chamber. This is thought to
prevent non-productive interactions andror to facilitate the folding of misfolded proteins.33,34 Release of
the folding-competent polypeptide from the hydrophobic walls allows folding to occur in solution.
In contrast, in the PapD-like chaperone system, pilus
subunits may fold directly on the chaperone template
and remain bound to the chaperone in their fully
folded states until they are assembled into a pilus at
the usher. Also, the DnaJrDnaKrGrpE and
GroELrGroES systems require ATP hydrolysis, while
the PapD-like chaperones function in the absence of
known cellular energy sources.35 Finally, the cytoplasmic and periplasmic chaperones differ in how
they facilitate folding. Both the DnaJrDnaKrGrpE
and GroELrGroES systems appear to prevent or
overcome the misfolding of proteins, rather than
contribute steric information during substrate folding.33 PapD-like chaperones, on the other hand, may
contribute steric information during the folding of
their substrates by providing an integral part of their
Ig fold. In this model, the complete information
required to produce a correctly folded Ig domain
would reside not in a single polypeptide chain but
rather in two distinct polypeptides.27
The various surface organelles assembled by Gramnegative bacteria, including pili, flagella, and other
macromolecular structures, have to withstand the
considerable forces that they experience in carrying
out their functions. A flagellum that breaks apart
daring the first stroke is of little use to the cell. A
pilus that breaks upon attachment loses its adhesiveness. The proposed pilus structure explains how such
a sturdy organelle can be built. The contribution of a
portion of the fold from one molecule to another, as
in the pilus model, produces a very tight interaction,
one that can be repeated over many molecules to
produce large structures. Protein polymerization by
domain swapping could also lead to the formation of
robust macromolecular assemblies.36 Indeed, any relatively strong interaction between two molecules that
can be repeated over a network of molecules in one
or more dimensions could be used to build an organelle. Many variations of such interactions could be
imagined to produce different structures. Such interactions might play a role in the formation of detrimental structures as well, for example the amyloid
fibers that characterize a variety of human diseases.
The coordinated assembly of such organelles, however, requires that the cell allow the subunits to
interact only at the site of assembly, since interactions
elsewhere might be non-productive. In pilus biogenesis, the PapD-like chaperone assures that subunits
interact with each other only at the usher. The FlgN
Table 2. Partial list of chaperones involved in organelle biogenesis
Organelle
Representative
chaperone
Pilus
CS1 pilus family
PapD
CooB
Curli
Flagellum
Flagellum
Flagellum
Type II secretion
system
Type III secretion
system
Type III secretion
system
Type III secretion
system
Organelle subunit
Reference
2,17, Table 1 herein
Reviewed in ref 39
CsgG?
FlgN
FliT?
FliJ
PulS
Pilus subunits
CooA, CooD Žpilus subunits.
CooC Žouter membrane protein.
CsgA,CsgB
FlgK, FlgL Žhook associated proteins.
FliD Žfilament cap protein.
FlgD, FlgE Žhook proteins., FliE?
PulD Žouter membrane protein.
SycD
YopB, YopD
43,44
YscB
YopN
45
VirG?
YscC Žouter membrane channel protein.
46
40
37
37
41
42
Notes. Only representative chaperones from homologous families are listed. Chaperones may or may not be part of the
final assembled organelle.
32
Chaperones and pilus biogenesis
12. Jones CH, Danese PN, Pinkner JS, Silhavey TJ, Hultgren SJ
Ž1997. The chaperone-assisted membrane release and folding
pathway is sensed by two signal transduction systems. EMBO J
16:6394᎐6406
13. Kuehn MJ, Normark S, Hultgren SJ Ž1991. Immunoglobulinlike PapD chaperone caps and uncaps interactive surfaces of
nascently translocated pilus subunits. Proc Natl Acad Sci USA
88:10586᎐10590
14. Bullitt E, Jones CH, Striker R, Soto G, Jacob-Dubuisson F,
Pinkner J, Wick MJ, Makowski L, Hultgren SJ Ž1996. Development of pilus organelle subassemblies in vitro depends on
chaperone uncapping of a beta zipper. Proc Natl Acad Sci
USA 93:12890᎐12895
15. Kuehn MJ, Ogg DJ, Kihlberg J, Slonim LN, Flemmer K,
Bergfors, T, Hultgren SJ Ž1993. Structural basis of pilus
subunit recognition by the PapD chaperone. Science
262:1234᎐1241
16. Soto GE, Dodson KW, Ogg D, Liu C, Heuser J, Knight S,
Kihlberg J, Jones CH, Hultgren SJ Ž1998. Periplasmic chaperone recognition motif of subunits mediates quaternary interactions in the pilus. EMBO J 17:6155᎐6167
17. Thanassi DG, Saulino ET, Hultgren SJ Ž1998. The chaperonerusher pathway: a major terminal branch of the general
secretory pathway. Curr Opin Microbiol 1:223᎐231
18. Dodson KW, Jacob-Dubuisson F, Striker RT, Hultgren SJ
Ž1993. Outer membrane PapC molecular usher discriminately recognizes periplamic chaperone᎐pilus subunit complexes. Proc Natl Acad Sci USA 90:3670᎐3674
19. Thanassi DG, Saulino ET, Lombardo M-J, Roth R, Heuser J,
Hultgren SJ Ž1998. The PapC usher forms an oligomeric
channel: implications for pilus biogenesis across the outer
membrane. Proc Natl Acad Sci USA 95:3146᎐3151
20. Saulino ET, Thanassi DG, Pinkner JS, Hultgren SJ Ž1998.
Ramifications of kinetic partitioning on usher-mediated pilus
biogenesis. EMBO J 17:2177᎐2185
21. Raivio TL, Silhavy TJ Ž1999. The sigmaE and Cpx regulatory
pathways: overlapping but distinct envelope stress responses.
Curr Opin Microbiol 2:159᎐165
22. Danese PN, Silhavy TJ Ž1997. The sigmaŽE. and Cpx signal
transduction systems control the synthesis of periplasmic protein-folding enzymes in Escherichia coli. Genes Dev
11:1183᎐1193
23. Danese PN, Snyder WB, Cosma CL, Davis LJ, Silhavy TJ
Ž1995. The Cpx two-component signal transduction pathway
of Escherichia coli regulates transcription of the gene specifying the stress inducible periplasmic protease DegP. Genes
Dev 9:387᎐398
24. Jacob-Dubuisson F, Pinkner J, Xu Z, Striker R, Padmanhaban
A, Hultgren SJ Ž1994. PapD chaperone function in pilus
biogenesis depends on oxidant and chaperone-like activities
of DsbA. Proc Natl Acad Sci USA 91:11552᎐11556
25. Holmgren A, Branden C-I Ž1989. Crystal structure of chaperone protein PapD reveals an immunoglobulin fold. Nature
342:248᎐251
26. Pellecchia M, Guntert P, Glockshuber R, Wuthrich K Ž1998.
NMR solution structure of the periplasmic chaperone FimC.
Nat Struct Biol 5:885᎐890
27. Choudhury D, Thompson A, Stojanoff V, Langermann S,
Pinkner J, Hultgren SL, Knight SD Ž1999. X-ray structure of
the FimC᎐FimH chaperone᎐adhesin complex from uropathogenic Escherichia coli. Science 285:1061᎐1066
28. Sauer FG, Futterer K, Pinkner JS, Dodson K, Hultgren SJ,
Waksman G Ž1999. Structural basis of chaperone function
and pilus biogenesis. Science 285:1058᎐1061
29. Slonim LN, Pinkner JS, Branden C-I, Hultgren SJ Ž1992.
Interactive surface in the PapD chaperone cleft is conserved
in pilus chaperone superfamily and essential in subunit
recognition and assembly. EMBO J 11:4747᎐4756
and FliT chaperones have been proposed to function
analogously in flagellar biogenesis.37 Thus, one common function of the growing number of chaperones
known to be involved in organelle biogenesis ŽTable
2. may be to regulate subunit assembly. By capping
the interactive surfaces of subunits until they reach
the appropriate assembly site, chaperones would
guarantee that organelle assembly proceeds in an
orderly fashion.
Acknowledgements
SJH is supported by NIH grants RO1DK51406 and
RO1AI29549, GW by NIH grant RO1GM54033, and SDK
by grants from the Swedish Research Council NFR and the
Swedish Foundation for Strategic Research ŽStructural Biology Network.. FGS was supported by an NSF Predoctoral
Fellowship.
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