%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Ruchi Jain, Oleksii Sliusarenko, Barbara I. Kazmierczak
Interaction of the cyclic-di-GMP binding protein FimX and the Type 4 pilus assembly ATPase promotes pilus assembly
www.plospathogens.org
www.plospathogens.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 14 0 R/Contents 15 0 R/TrimBox[0 0 612 792]>>
endobj
14 0 obj
[16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R 35 0 R]
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref001)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref003)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref004)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref006)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref007)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref008)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref009)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref010)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref012)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref013)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref014)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref006)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref010)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref015)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref016)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref017)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref019)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref020)>>
endobj
34 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006594.ref021)>>
endobj
35 0 obj
<>/Border[0 0 0]/A 36 0 R>>
endobj
36 0 obj
<>
endobj
15 0 obj
[37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R 52 0 R 53 0 R 54 0 R 55 0 R]
endobj
37 0 obj
<>stream
q
0.955 g
0 w
199.9998 713.9999 m
575.9997 713.9999 l
575.9997 585.0003 l
199.9998 585.0003 l
f*
0.83 0.64 0.02 0 k
277.0583 497.9339 m
281.8205 497.9339 l
h
f*
287.0362 497.9339 m
291.7417 497.9339 l
h
f*
405.6945 484.8945 m
410.4567 484.8945 l
h
f*
415.6157 484.8945 m
420.378 484.8945 l
h
f*
276.2079 432.9071 m
280.9701 432.9071 l
h
f*
553.3795 406.9417 m
558.1417 406.9417 l
h
f*
562.6205 406.9417 m
567.3827 406.9417 l
h
f*
543.515 367.937 m
553.0394 367.937 l
h
f*
558.1984 367.937 m
567.7228 367.937 l
h
f*
427.9748 302.9102 m
437.4425 302.9102 l
h
f*
441.9213 302.9102 m
451.4457 302.9102 l
h
f*
510.0661 224.9008 m
514.8283 224.9008 l
h
f*
222.8598 172.9134 m
232.3843 172.9134 l
h
f*
453.0331 146.948 m
462.5575 146.948 l
h
f*
466.9795 146.948 m
476.5039 146.948 l
h
f*
538.8661 120.926 m
548.3906 120.926 l
h
f*
553.5496 120.926 m
563.074 120.926 l
h
f*
234.0283 94.9039 m
243.4961 94.9039 l
h
f*
491.074 81.9213 m
500.5984 81.9213 l
h
f*
0 g
1 j
1 J
10 0 0 10 209.9905 696.9826 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(intoxicate)Tj
4.1555 0 Td
(host)Tj
1.9106 0 Td
(tissues,)Tj
3.0443 0 Td
(and)Tj
1.7348 0 Td
(elaborate)Tj
3.8608 0 Td
(multicellular)Tj
5.3008 0 Td
(structures)Tj
4.1839 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(biofilms.)Tj
3.7077 0 Td
(Assembly)Tj
-30.9711 -1.2982 Td
(and)Tj
1.7291 0 Td
(retraction)Tj
4.1669 0 Td
(are)Tj
1.4456 0 Td
(powered)Tj
3.6737 0 Td
(by)Tj
1.1849 0 Td
(specific)Tj
3.1918 0 Td
(ATPases,)Tj
3.8777 0 Td
(PilB)Tj
1.8709 0 Td
(and)Tj
1.7291 0 Td
(PilT)Tj
1.9049 0 Td
(respectively,)Tj
5.108 0 Td
(but)Tj
1.5534 0 Td
(the)Tj
1.474 0 Td
(man-)Tj
-32.91 -1.2983 Td
(ner)Tj
1.5647 0 Td
(in)Tj
1.0374 0 Td
(which)Tj
2.6476 0 Td
(their)Tj
2.1089 0 Td
(activity)Tj
3.1181 0 Td
(is)Tj
0.8448 0 Td
(coordinated)Tj
5.0569 0 Td
(is)Tj
0.8504 0 Td
(still)Tj
1.6384 0 Td
(poorly)Tj
2.8233 0 Td
(understood.)Tj
5.0457 0 Td
(In)Tj
1.1055 0 Td
(this)Tj
1.6781 0 Td
(work,)Tj
2.5001 0 Td
(we)Tj
1.3323 0 Td
(pro-)Tj
-33.3522 -1.3039 Td
(vide)Tj
1.8935 0 Td
(evidence)Tj
3.7133 0 Td
(that)Tj
1.7802 0 Td
(a)Tj
0.652 0 Td
(high-affinity)Tj
5.2043 0 Td
(c-di-GMP)Tj
4.303 0 Td
(binding)Tj
3.3562 0 Td
(protein)Tj
3.1521 0 Td
(of)Tj
/F11 1 Tf
1.0148 0 Td
[()18()-3()2()4()4()11()6()11()6( )]TJ
5.5672 0 Td
[( )6()2(\n)-9()10()-8()12()6()7()-3( )]TJ
/F6 1 Tf
(,)Tj
-30.6366 -1.2983 Td
(FimX,)Tj
2.7155 0 Td
(interacts)Tj
3.6454 0 Td
(with)Tj
1.9955 0 Td
(the)Tj
1.4684 0 Td
(ATPase)Tj
3.2938 0 Td
(PilB)Tj
1.8709 0 Td
(and)Tj
1.7348 0 Td
(promotes)Tj
4.0195 0 Td
(PilB-dependent)Tj
6.4629 0 Td
(assembly)Tj
3.8268 0 Td
(of)Tj
1.0148 0 Td
(T4P.)Tj
-32.0483 -1.2982 Td
(Live)Tj
1.9048 0 Td
(cell)Tj
1.5591 0 Td
(imaging)Tj
3.4866 0 Td
(of)Tj
1.0148 0 Td
(twitching)Tj
4.0024 0 Td
(bacteria)Tj
3.3789 0 Td
(shows)Tj
2.6589 0 Td
(that)Tj
1.7802 0 Td
(FimX)Tj
2.4831 0 Td
(localizes)Tj
3.5433 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(leading)Tj
3.1351 0 Td
(pole)Tj
1.9106 0 Td
(of)Tj
-33.3522 -1.3039 Td
(motile)Tj
/F11 1 Tf
2.7836 0 Td
[()]TJ
/F6 1 Tf
(.)Tj
/F11 1 Tf
0.9921 0 Td
[( )6()2(\n)-9()10()-8()12()6()7()-3( )]TJ
/F6 1 Tf
4.4787 0 Td
(and)Tj
1.7291 0 Td
(that)Tj
1.7802 0 Td
(its)Tj
1.1451 0 Td
(recruitment)Tj
4.989 0 Td
(requires)Tj
3.4752 0 Td
(both)Tj
2.058 0 Td
(components)Tj
5.176 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(T4P)Tj
1.8652 0 Td
(assem-)Tj
-32.9553 -1.2983 Td
(bly)Tj
1.4286 0 Td
(machine)Tj
3.6623 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4684 0 Td
(PilB)Tj
1.8708 0 Td
(ATPase.)Tj
3.5206 0 Td
(Our)Tj
1.8652 0 Td
(work)Tj
2.2791 0 Td
(highlights)Tj
4.1725 0 Td
(a)Tj
0.652 0 Td
(novel)Tj
2.3981 0 Td
(regulatory)Tj
4.32 0 Td
(strategy)Tj
-29.3724 -1.2983 Td
(employed)Tj
4.1385 0 Td
(by)Tj
/F11 1 Tf
1.1849 0 Td
[()]TJ
/F6 1 Tf
(.)Tj
/F11 1 Tf
0.9921 0 Td
[( )6()2(\n)-9()10()-8()12()6()7()-3( )]TJ
/F6 1 Tf
4.4787 0 Td
(to)Tj
1.0205 0 Td
(control)Tj
3.1237 0 Td
(assembly)Tj
3.8268 0 Td
(of)Tj
1.0148 0 Td
(this)Tj
1.6724 0 Td
(broadly)Tj
3.2712 0 Td
(conserved)Tj
4.2576 0 Td
(virulence)Tj
3.9061 0 Td
(factor.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 541.9842 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 524.9763 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Type)Tj
2.228 0 Td
(IV)Tj
1.2529 0 Td
(pili)Tj
1.5193 0 Td
(\(T4P\))Tj
2.5455 0 Td
(are)Tj
1.4457 0 Td
(long)Tj
1.9899 0 Td
(\(520)Tj
/F12 1 Tf
2.5001 0 Td
[()]TJ
/F6 1 Tf
(m\),)Tj
2.1147 0 Td
(flexible)Tj
3.084 0 Td
(surface)Tj
3.0501 0 Td
(structures)Tj
4.1839 0 Td
(that)Tj
1.7802 0 Td
(perform)Tj
3.5149 0 Td
(a)Tj
0.6576 0 Td
(variety)Tj
2.9197 0 Td
(of)Tj
-34.7865 -1.2982 Td
(functionsmotility,)Tj
8.2941 0 Td
(adherence,)Tj
4.5524 0 Td
(and)Tj
1.7291 0 Td
(DNA)Tj
2.3754 0 Td
(uptakein)Tj
4.6602 0 Td
(Gram-negative)Tj
6.2248 0 Td
(and)Tj
1.7291 0 Td
(-positive)Tj
3.668 0 Td
(bacteria,)Tj
-33.2331 -1.2983 Td
(as)Tj
1.0147 0 Td
(well)Tj
1.8199 0 Td
(as)Tj
1.0148 0 Td
(Archaea)Tj
3.5149 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(].)Tj
2.5965 0 Td
(T4P)Tj
1.8652 0 Td
(are)Tj
1.4513 0 Td
(capable)Tj
3.2032 0 Td
(of)Tj
1.0148 0 Td
(generating)Tj
4.4673 0 Td
(significant)Tj
4.3881 0 Td
(force)Tj
2.2336 0 Td
(\(30100)Tj
3.4526 0 Td
(pN\))Tj
1.8142 0 Td
(through)Tj
-33.8511 -1.3039 Td
(the)Tj
1.4683 0 Td
(rapid)Tj
2.3357 0 Td
(retraction)Tj
4.1669 0 Td
(of)Tj
1.0148 0 Td
(an)Tj
1.2019 0 Td
(anchored)Tj
3.9798 0 Td
(pilin)Tj
2.0693 0 Td
(multimer)Tj
3.9912 0 Td
([)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
2.5965 0 Td
(Recurrent)Tj
4.2292 0 Td
(cycles)Tj
2.5512 0 Td
(of)Tj
1.0148 0 Td
(pilus)Tj
2.1373 0 Td
(assembly)Tj
-32.7569 -1.2983 Td
(and)Tj
1.7291 0 Td
(disassembly,)Tj
5.21 0 Td
(driven)Tj
2.812 0 Td
(by)Tj
1.1792 0 Td
(distinct)Tj
3.2144 0 Td
(assembly)Tj
3.8268 0 Td
(and)Tj
1.7291 0 Td
(retraction)Tj
4.1612 0 Td
(ATPases,)Tj
3.8835 0 Td
(allow)Tj
2.3357 0 Td
(for)Tj
1.3833 0 Td
(directed)Tj
3.4866 0 Td
(bacte-)Tj
-34.9509 -1.2982 Td
(rial)Tj
1.5363 0 Td
(movement)Tj
4.5184 0 Td
(across)Tj
2.6759 0 Td
(surfaces.)Tj
3.634 0 Td
(This)Tj
1.9899 0 Td
(twitching)Tj
4.388 0 Td
(motility)Tj
3.7701 0 Td
(is)Tj
0.8504 0 Td
(critical)Tj
2.9536 0 Td
(for)Tj
1.3833 0 Td
(bacterial)Tj
3.6227 0 Td
(colonization)Tj
5.1874 0 Td
(of)Tj
-36.51 -1.2983 Td
(surfaces)Tj
3.4072 0 Td
(and)Tj
1.7291 0 Td
(required)Tj
3.6397 0 Td
(for)Tj
1.3889 0 Td
(formation)Tj
4.2576 0 Td
(and)Tj
1.7348 0 Td
(maturation)Tj
4.7225 0 Td
(of)Tj
1.0148 0 Td
(biofilms)Tj
3.4866 0 Td
(by)Tj
1.1792 0 Td
(pathogens)Tj
4.303 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
/F11 1 Tf
1.0148 0 Td
[()18()-3()2()4()4(\r)]TJ
-33.9361 -1.3039 Td
[()6()11()6( )]TJ
2.8062 0 Td
[( )6()2(\n)-9()10()-8()12()6()7()-3( )]TJ
/F6 1 Tf
4.4731 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
-6.0831 -1.2983 Td
(The)Tj
1.7858 0 Td
(machinery)Tj
4.49 0 Td
(required)Tj
3.6397 0 Td
(for)Tj
1.3833 0 Td
(T4P)Tj
1.8652 0 Td
(assembly)Tj
3.8267 0 Td
(has)Tj
1.5477 0 Td
(been)Tj
2.1203 0 Td
(extensively)Tj
4.5865 0 Td
(studied)Tj
3.1521 0 Td
(in)Tj
1.0374 0 Td
(several)Tj
2.931 0 Td
(bacterial)Tj
-33.5619 -1.2982 Td
(organisms,)Tj
4.5807 0 Td
(including)Tj
/F11 1 Tf
4.0422 0 Td
[()]TJ
/F6 1 Tf
(.)Tj
/F11 1 Tf
0.9921 0 Td
[( )6()2(\n)-9()10()-8()12()6()7()-3( )]TJ
4.4731 0 Td
[()23( )]TJ
/F6 1 Tf
(,)Tj
/F11 1 Tf
2.1316 0 Td
[()28()2()-4()10()-3()2(\n)-9()4( )]TJ
3.736 0 Td
[()2()11()6()11(\n)-9(\n)8()6()4()7( )6()]TJ
/F6 1 Tf
5.057 0 Td
(and)Tj
/F11 1 Tf
1.7291 0 Td
[()47()-4()4()7()4()7()1()-4()]TJ
4.8926 0 Td
[()-4( )16()22()10()18()-4()]TJ
/F6 1 Tf
3.3619 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2642 0 Td
(9)Tj
0 g
(].)Tj
-36.2605 -1.304 Td
(Electron)Tj
3.6056 0 Td
(cryo-tomography)Tj
7.2283 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(T4a)Tj
1.7405 0 Td
(pilus)Tj
2.1373 0 Td
(machines)Tj
4.0251 0 Td
(of)Tj
/F11 1 Tf
1.0148 0 Td
[()]TJ
/F6 1 Tf
(.)Tj
/F11 1 Tf
1.3153 0 Td
[()-4( )16()22()10()18()-4()]TJ
/F6 1 Tf
3.3619 0 Td
(and)Tj
/F11 1 Tf
1.7291 0 Td
[()1()6()2(\n)-9()18()-4()]TJ
3.7077 0 Td
[()10()6()2(\n)-9()6()11()10()18(\r)]TJ
-32.3544 -1.2982 Td
[()12()-4()]TJ
/F6 1 Tf
(,)Tj
1.5363 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.474 0 Td
(T4b)Tj
1.8142 0 Td
(toxin-coregulated)Tj
7.302 0 Td
(pilus)Tj
2.1373 0 Td
(machine)Tj
3.668 0 Td
(of)Tj
/F11 1 Tf
1.0148 0 Td
[()53()14()11(\n)-9()4()]TJ
2.7156 0 Td
[()13()6()10()4()2(\n)20( )6()]TJ
/F6 1 Tf
3.4299 0 Td
(has)Tj
1.5477 0 Td
(revealed)Tj
3.5206 0 Td
(three-dimen-)Tj
-31.8895 -1.2983 Td
(sional)Tj
/F11 1 Tf
2.5851 0 Td
[()12()]TJ
1.0148 0 Td
[()10()14()7()]TJ
/F6 1 Tf
1.6384 0 Td
(structures)Tj
4.184 0 Td
(that)Tj
1.7801 0 Td
(are)Tj
1.4513 0 Td
(consistent)Tj
4.252 0 Td
(with)Tj
2.0012 0 Td
(models)Tj
3.1011 0 Td
(proposed)Tj
3.9515 0 Td
(for)Tj
1.3889 0 Td
(these)Tj
2.2564 0 Td
(complexes)Tj
4.405 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(].)Tj
-34.0098 -1.3039 Td
(In)Tj
1.1055 0 Td
(each,)Tj
2.2563 0 Td
(an)Tj
1.2019 0 Td
(outer)Tj
2.3471 0 Td
(membrane)Tj
4.5694 0 Td
(\(OM\))Tj
2.5398 0 Td
(secretin)Tj
3.3335 0 Td
(\()Tj
/F11 1 Tf
[()23( )]TJ
/F6 1 Tf
1.5988 0 Td
(PilQ\))Tj
2.3754 0 Td
(and)Tj
1.7291 0 Td
(pilotin)Tj
2.8743 0 Td
(\()Tj
/F11 1 Tf
[()23( )]TJ
/F6 1 Tf
1.5931 0 Td
(PilF\))Tj
2.16 0 Td
(are)Tj
1.4513 0 Td
(required)Tj
3.6397 0 Td
(for)Tj
1.3833 0 Td
(an)Tj
-36.1585 -1.2983 Td
(emerging)Tj
4.0024 0 Td
(pilin)Tj
2.0693 0 Td
(multimer)Tj
3.9912 0 Td
(to)Tj
1.0261 0 Td
(exit)Tj
1.6724 0 Td
(the)Tj
1.4684 0 Td
(cell)Tj
1.559 0 Td
(envelope.)Tj
3.9912 0 Td
(Electron)Tj
3.6113 0 Td
(cryo-tomography)Tj
7.2283 0 Td
(structures)Tj
4.1839 0 Td
(show)Tj
-34.8035 -1.2982 Td
(an)Tj
1.2018 0 Td
(inner)Tj
2.3811 0 Td
(membrane)Tj
4.5638 0 Td
(\(IM\))Tj
2.1316 0 Td
(protein)Tj
3.1578 0 Td
(\()Tj
/F11 1 Tf
[()23( )]TJ
/F6 1 Tf
1.593 0 Td
(PilC\))Tj
2.2961 0 Td
(aligned)Tj
3.1294 0 Td
(with)Tj
2.0013 0 Td
(periplasmic)Tj
4.8642 0 Td
(rings)Tj
2.2337 0 Td
(assigned)Tj
3.6113 0 Td
(to)Tj
/F11 1 Tf
1.0205 0 Td
[()23( )]TJ
/F6 1 Tf
1.2585 0 Td
(PilN,)Tj
-35.4441 -1.2983 Td
(PilO)Tj
2.0352 0 Td
(and)Tj
1.7348 0 Td
(PilP;)Tj
2.075 0 Td
(these)Tj
2.2563 0 Td
(three)Tj
2.262 0 Td
(proteins)Tj
3.515 0 Td
(are)Tj
1.4456 0 Td
(proposed)Tj
3.9515 0 Td
(to)Tj
1.0262 0 Td
(form)Tj
2.2053 0 Td
(a)Tj
0.6576 0 Td
(scaffold)Tj
3.2939 0 Td
(that)Tj
1.7801 0 Td
(links)Tj
2.1373 0 Td
(the)Tj
1.4684 0 Td
(outer)Tj
2.347 0 Td
(mem-)Tj
-34.1912 -1.3039 Td
(brane)Tj
2.5058 0 Td
(pore)Tj
2.0352 0 Td
(to)Tj
1.0262 0 Td
(cytoplasmic)Tj
4.9719 0 Td
(components,)Tj
5.4028 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
/F11 1 Tf
1.0148 0 Td
[()23( )]TJ
/F6 1 Tf
1.2529 0 Td
(PilM)Tj
2.1884 0 Td
([)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(14)Tj
0 g
(].)Tj
1.7348 0 Td
(A)Tj
0.907 0 Td
(prepilin)Tj
3.3789 0 Td
(peptidase)Tj
3.9855 0 Td
(\()Tj
/F11 1 Tf
[()23( )]TJ
/F6 1 Tf
-34.1969 -1.2983 Td
(PilD\))Tj
2.3697 0 Td
(processes)Tj
3.9685 0 Td
(the)Tj
1.4683 0 Td
(major)Tj
2.6079 0 Td
(pilin)Tj
2.0636 0 Td
(\()Tj
/F11 1 Tf
[()23( )]TJ
/F6 1 Tf
1.5987 0 Td
(PilA\))Tj
2.3131 0 Td
(and)Tj
1.7348 0 Td
(a)Tj
0.6519 0 Td
(number)Tj
3.4186 0 Td
(of)Tj
1.0148 0 Td
(minor)Tj
2.7326 0 Td
(pilins)Tj
2.4264 0 Td
(before)Tj
2.7383 0 Td
(they)Tj
1.9275 0 Td
(can)Tj
1.6271 0 Td
(be)Tj
-34.6618 -1.2982 Td
(incorporated)Tj
5.4141 0 Td
(into)Tj
1.8425 0 Td
(the)Tj
1.4683 0 Td
(base)Tj
1.9446 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(growing)Tj
3.5263 0 Td
(T4P)Tj
1.8652 0 Td
(by)Tj
1.1792 0 Td
(an)Tj
1.2075 0 Td
(assembly)Tj
3.8268 0 Td
(ATPase)Tj
3.2881 0 Td
(\()Tj
/F11 1 Tf
[()23( )]TJ
/F6 1 Tf
1.5988 0 Td
(PilB\).)Tj
-28.454 -1.304 Td
(Despite)Tj
3.2484 0 Td
(this)Tj
1.6725 0 Td
(wealth)Tj
2.8346 0 Td
(of)Tj
1.0148 0 Td
(knowledge)Tj
4.5467 0 Td
(about)Tj
2.4888 0 Td
(the)Tj
1.4741 0 Td
(components)Tj
5.1703 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(T4P)Tj
1.8652 0 Td
(assembly)Tj
3.8268 0 Td
(machinery,)Tj
4.7168 0 Td
(it)Tj
-36.544 -1.2982 Td
(is)Tj
0.8447 0 Td
(still)Tj
1.6384 0 Td
(not)Tj
1.576 0 Td
(clear)Tj
2.1203 0 Td
(how)Tj
1.9389 0 Td
(the)Tj
1.4684 0 Td
(activity)Tj
3.1181 0 Td
(of)Tj
1.0147 0 Td
(the)Tj
1.4684 0 Td
(assembly)Tj
3.8267 0 Td
(\()Tj
/F11 1 Tf
[()23( )]TJ
/F6 1 Tf
1.5931 0 Td
(PilB\))Tj
2.2167 0 Td
(or)Tj
1.0941 0 Td
(disassembly)Tj
4.9833 0 Td
(\()Tj
/F11 1 Tf
[()23( )]TJ
/F6 1 Tf
1.5987 0 Td
(PilT)Tj
1.8992 0 Td
(and)Tj
1.7348 0 Td
(PilU\))Tj
-34.1345 -1.2983 Td
(ATPases)Tj
3.651 0 Td
(is)Tj
0.8503 0 Td
(coordinated)Tj
5.057 0 Td
(to)Tj
1.0205 0 Td
(achieve)Tj
3.1748 0 Td
(net)Tj
1.491 0 Td
(T4P)Tj
1.8652 0 Td
(extension)Tj
4.0648 0 Td
(or)Tj
1.0999 0 Td
(retraction.)Tj
4.388 0 Td
(As)Tj
1.2642 0 Td
(the)Tj
1.4683 0 Td
(multiple)Tj
3.566 0 Td
(T4P)Tj
1.8652 0 Td
(pres-)Tj
-34.8262 -1.3039 Td
(ent)Tj
1.491 0 Td
(at)Tj
0.9524 0 Td
(a)Tj
0.652 0 Td
(single)Tj
2.5341 0 Td
(bacterial)Tj
3.6227 0 Td
(pole)Tj
1.9162 0 Td
(extend)Tj
2.9026 0 Td
(and)Tj
1.7292 0 Td
(retract)Tj
2.8403 0 Td
(independently)Tj
5.981 0 Td
(of)Tj
1.0148 0 Td
(one)Tj
1.6951 0 Td
(another)Tj
3.3336 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(],)Tj
1.5987 0 Td
(regulation)Tj
-32.2637 -1.2983 Td
(must)Tj
2.228 0 Td
(occur)Tj
2.4718 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(level)Tj
2.0126 0 Td
(of)Tj
1.0148 0 Td
(individual)Tj
4.2916 0 Td
(ATPase)Tj
3.2882 0 Td
(recruitment)Tj
4.9946 0 Td
(to)Tj
1.0262 0 Td
(or)Tj
1.0998 0 Td
(activation)Tj
4.1499 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4684 0 Td
(T4P)Tj
1.8651 0 Td
(base.)Tj
2.1714 0 Td
(The)Tj
-35.4555 -1.2982 Td
(recent)Tj
2.7099 0 Td
(electron)Tj
3.4582 0 Td
(cryo-tomography)Tj
7.2283 0 Td
(structure)Tj
3.8267 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
/F11 1 Tf
1.4684 0 Td
[()]TJ
/F6 1 Tf
(.)Tj
/F11 1 Tf
1.3152 0 Td
[()-4( )16()22()10()18()-4()]TJ
/F6 1 Tf
3.3619 0 Td
(type)Tj
1.9162 0 Td
(IVa)Tj
1.6895 0 Td
(assembly)Tj
3.8267 0 Td
(machinery)Tj
-31.8158 -1.304 Td
(supports)Tj
3.6793 0 Td
(this,)Tj
1.8992 0 Td
(as)Tj
1.0148 0 Td
(PilB)Tj
1.8708 0 Td
(and)Tj
1.7348 0 Td
(PilT)Tj
1.8992 0 Td
(appear)Tj
2.9197 0 Td
(to)Tj
1.0261 0 Td
(bind)Tj
2.0693 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.652 0 Td
(mutually)Tj
3.7757 0 Td
(exclusive)Tj
3.8097 0 Td
(fashion)Tj
3.1521 0 Td
(to)Tj
1.0262 0 Td
(PilC)Tj
1.9559 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(T4P)Tj
-35.943 -1.2982 Td
(base)Tj
1.9445 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(].)Tj
/F11 1 Tf
-0.7483 -1.2983 Td
[()]TJ
/F6 1 Tf
(.)Tj
/F11 1 Tf
0.9978 0 Td
[( )6()2(\n)-9()10()-8()12()6()7()-3( )]TJ
/F6 1 Tf
4.473 0 Td
(T4P)Tj
1.8652 0 Td
(assembly)Tj
3.8267 0 Td
(requires)Tj
3.4753 0 Td
(two)Tj
1.7064 0 Td
(additional)Tj
4.2803 0 Td
(proteins,)Tj
3.7417 0 Td
(FimX)Tj
2.4832 0 Td
(and)Tj
1.7291 0 Td
(PilZ;)Tj
2.1203 0 Td
(homologs)Tj
4.1612 0 Td
(of)Tj
-36.0564 -1.2982 Td
(these)Tj
2.2506 0 Td
(proteins)Tj
3.515 0 Td
(are)Tj
1.4513 0 Td
(not)Tj
1.5704 0 Td
(present)Tj
3.1634 0 Td
(in)Tj
/F11 1 Tf
1.0375 0 Td
[()]TJ
/F6 1 Tf
(.)Tj
/F11 1 Tf
1.3153 0 Td
[()-4( )16()22()10()18()-4()]TJ
/F6 1 Tf
3.3619 0 Td
(or)Tj
/F11 1 Tf
1.0998 0 Td
[()]TJ
/F6 1 Tf
(.)Tj
/F11 1 Tf
1.1395 0 Td
[()2()11()6()11(\n)-9(\n)8()6()4()7( )6()]TJ
/F6 1 Tf
5.057 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(16)Tj
0 g
(].)Tj
1.7404 0 Td
(FimX)Tj
2.4832 0 Td
(is)Tj
0.8504 0 Td
(a)Tj
0.6519 0 Td
(degenerate)Tj
-32.4224 -1.304 Td
(GGDEF/EAL)Tj
5.6068 0 Td
(domain)Tj
3.3222 0 Td
(protein)Tj
3.1521 0 Td
(that)Tj
1.7802 0 Td
(binds)Tj
2.4321 0 Td
(cyclic-di-GMP)Tj
6.1171 0 Td
(via)Tj
1.3776 0 Td
(its)Tj
1.1452 0 Td
(EAL)Tj
2.0126 0 Td
(domain;)Tj
3.549 0 Td
(the)Tj
1.4683 0 Td
(purified)Tj
3.4129 0 Td
(pro-)Tj
-35.3761 -1.2982 Td
(tein)Tj
1.7574 0 Td
(has)Tj
1.5421 0 Td
(no)Tj
1.2755 0 Td
(diguanylate)Tj
4.8473 0 Td
(cyclase)Tj
2.9877 0 Td
(activity)Tj
3.118 0 Td
(and)Tj
1.7292 0 Td
(exhibits)Tj
3.3335 0 Td
(weak)Tj
2.262 0 Td
(phosphodiesterase)Tj
7.5741 0 Td
(activity)Tj
3.1181 0 Td
([)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(].)Tj
-33.5449 -1.2983 Td
(PilZ,)Tj
2.1146 0 Td
(despite)Tj
3.0387 0 Td
(possessing)Tj
4.3937 0 Td
(the)Tj
1.4683 0 Td
(characteristic)Tj
5.5445 0 Td
(fold)Tj
1.7915 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(c-di-GMP)Tj
4.3086 0 Td
(receptor,)Tj
3.7814 0 Td
(fails)Tj
1.8142 0 Td
(to)Tj
1.0261 0 Td
(bind)Tj
2.0693 0 Td
(c-di-GMP)Tj
/F11 1 Tf
-33.0177 -1.3039 Td
[()12()]TJ
1.0147 0 Td
[()-13()14()7(\n)20()]TJ
/F6 1 Tf
2.0466 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(].)Tj
2.075 0 Td
(In)Tj
/F11 1 Tf
1.1055 0 Td
[()25( )16()22()10()6()11()6()11()6( )]TJ
5.7259 0 Td
[( )-4()11()6()11()4()4()12()-4()]TJ
/F6 1 Tf
4.6658 0 Td
(pv.)Tj
1.4174 0 Td
(citri)Tj
/F11 1 Tf
1.8425 0 Td
[()25( )6()]TJ
/F6 1 Tf
(,)Tj
2.5851 0 Td
(PilZ)Tj
1.8936 0 Td
(\(XAC1133\))Tj
4.8018 0 Td
(binds)Tj
2.4322 0 Td
(both)Tj
2.0579 0 Td
(PilB)Tj
1.8765 0 Td
(and)Tj
-35.5405 -1.2983 Td
(FimX)Tj
2.4888 0 Td
(\(XAC2398\),)Tj
5.0229 0 Td
(and)Tj
1.7348 0 Td
(this)Tj
1.6724 0 Td
(complex)Tj
3.6227 0 Td
(is)Tj
0.8447 0 Td
(proposed)Tj
3.9572 0 Td
(to)Tj
1.0204 0 Td
(regulate)Tj
3.4129 0 Td
(PilB)Tj
1.8709 0 Td
(activity)Tj
3.1181 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(].)Tj
2.0749 0 Td
(PilZ-FimX)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 144.5669 23.6976 re
W* n
q
144.5102 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 401.6125 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(FimX)Tj
2.5299 0 Td
(promotes)Tj
4.3229 0 Td
(T4P)Tj
2.0338 0 Td
(assemb)Tj
3.4442 0 Td
(ly)Tj
0.9283 0 Td
(via)Tj
1.474 0 Td
(the)Tj
1.5875 0 Td
(ATPase)Tj
3.7275 0 Td
(PilB)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
102.0472 34.9228 m
256.1953 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(Pathogens)Tj
4.9252 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://)Tj
2.9552 0 Td
(doi.org/10.13)Tj
5.7331 0 Td
(71/journal.p)Tj
5.1236 0 Td
(pat.1006)Tj
3.8198 0 Td
(594)Tj
0 g
2.6362 0 Td
(August)Tj
3.2811 0 Td
(30,)Tj
1.5874 0 Td
(2017)Tj
31.7483 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(23)Tj
/F9 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(funders)Tj
3.0472 0 Td
(had)Tj
1.5874 0 Td
(no)Tj
1.1693 0 Td
(role)Tj
1.6087 0 Td
(in)Tj
0.8929 0 Td
(study)Tj
2.2607 0 Td
(design,)Tj
2.8984 0 Td
(data)Tj
1.793 0 Td
(collection)Tj
-15.2576 -1.3748 Td
(and)Tj
1.5874 0 Td
(analysis,)Tj
3.4087 0 Td
(decision)Tj
3.2953 0 Td
(to)Tj
0.9496 0 Td
(publish,)Tj
3.1464 0 Td
(or)Tj
0.9993 0 Td
(preparation)Tj
4.4362 0 Td
(of)Tj
-17.8229 -1.3749 Td
(the)Tj
1.3677 0 Td
(manuscript.)Tj
/F8 1 Tf
-1.3677 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F9 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3748 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
38 0 obj
<>stream
endstream
endobj
39 0 obj
<>stream
endstream
endobj
40 0 obj
<>stream
endstream
endobj
41 0 obj
<>stream
endstream
endobj
42 0 obj
<>stream
endstream
endobj
43 0 obj
<>stream
endstream
endobj
44 0 obj
<>stream
endstream
endobj
45 0 obj
<>stream
endstream
endobj
46 0 obj
<>stream
endstream
endobj
47 0 obj
<>stream
endstream
endobj
48 0 obj
<>stream
endstream
endobj
49 0 obj
<>stream
endstream
endobj
50 0 obj
<>stream
endstream
endobj
51 0 obj
<>stream
endstream
endobj
52 0 obj
<>stream
endstream
endobj
53 0 obj
<>stream
endstream
endobj
54 0 obj
<>stream
endstream
endobj
55 0 obj
<>stream
BT
10.3394 77.8399 Td
(exist.)Tj
ET
Q
endstream
endobj
56 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 60 0 R/Contents 61 0 R/TrimBox[0 0 612 792]>>
endobj
59 0 obj
<>stream
x ME%Q#e(~$*)*TҀ,!ͨs"*!s
L!sq{o~γk]k{]zWlm!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`!`$_sC0C0C0C02 L0C 61C0C0C0C@00C Qao!`!`!`!HMd!`Fg!`!`!`!`q_!`B =^pNRT,BJ${W2X8d^_;4C0C0C0C %HMd!`ߛ9q"6&&&wJ?x'Nyxbc\'Ndtk."Ci{r"ccǒC0C0C0CH!<6C0HG9Uݻ{#zwd1طoƍA\pǎxd\b#rzسgƍ{w\غe˶~;D>thoQ%eC0C0C0C0R
)"4CHtba?fΘ1fԨ7}2=rdy>e`}6o"bདѭ۲eOr
,0C K9<_syM4P^ڵm۶VѣF߷/҄/;u;͝LܪewU^ݻ/_PRP+/oFjש駘ؑ#ʕk}?OT>l~-Չu^xc-YH^3dA@i=u5?XjJ~kWuݻ:7D^a6s+38;]1Tֵ?o30t*c\h{̠ٵcǖ͛ai\z\/jb
C0C0C !Y!`@UaG
G-[%K7#9moqalguV_߽s#G+Rj*W&;ו)sEȑqŏ+/|ՕWiՊRtJ0U%Z.XчJ7P˯+Xsm~sy'eN#_l߾O7sZΛ
1Ttԩ;vlۦЏ?;MrTC@_xbȏ={>٬YjxІիӌy뭯fܹ};mlT;+0C0C0N|3f!9i0n]xqc}sPpĔI?I͔)lY||&
m"O=w0X֝wN?,xy
:X8У/^dnɊ+e̙ؖ?䓋.{(TiӨG|M1tI+TPlYxN`3wHM
'N,^u˕`ueguWS38K.)|eJf.)Sh&p ONL0ɎG?ſ
&gy/0Unj>{^wuzd0瘎미jsgkWƍfL6)а\rԊjlՀ0ib=HϚ%K%j~5k ɳwgER9}0|ps;ճ^pn*g a17-' C?vZE$?#S&qsqyW;W./shTTg{d`ga!`!`$l3C4NCxuIpw}8X*a 6:vP!K*Yx=B毿zܹ!`;YS
ԭ[e:1)/Ud2e7_U?;h|w8bE ?_fݺ뮿-Zr6m`^Xݻv=sBJR^s7rcz^pD"&6t?bF:F|ɫ:=4!.T$NZwUE}'>S͚={dL$$Ճ0ϗ/C
arhf(гC0C0C@6C0H9<nL֯[Pp^{-fr(xr,-weֻW/hj&y;xx8ggc=+`PC}CÒƝk]=nVh(lݲï
+^uU*cɹ_Wͱ=?kV<'7Rƹ
/B]ܹ6iZ:Άy ^۾;]KF;\_SQ<04VG[#]G-gͿgm#>0Bt饗{TS!`!`@J |Z0Cxmv"o
* w4dࢁͳ0g'V\}E`S{8so_lQ%e~9.˕]vj<1U k/'6yP7UҥYlT-6}2|=7Oq1nXÞ^>t{,JQ5y|ɓǣ!xNA|NW=O+W{
,6,i.d#Kb+0N~DpHTSKxR@x№喢h"̹5V^)"d},20(3o/6hN=66 1\JFYBrqLTLjPCV'6S)Ha0#&4po5Xn S%!`!`A0C r<$]O&JO?jmWReҤIX}{M6v\\xgB`ݚ5؟ϟ0Q-s]xp~M7%^:'J}[! Ȉ/WT 17pCŋ-Yklsd$?NSd6>6G+І\;U4:kc<W$FJHRG"h$h@;DJeC!GL' [^+NJ2eׯ?$/}¼Sǎ(DۤYr\8:B֪Ukڵ-gdɒx9M;2wM7.]|pÆx~w 0,ǎ\2_Щ|ʀB/WnUspJ_|̙1͗7_~)Tf+m*Thuw堄L\sߩ'V,;LcLPUs~nJD!AϚ~DXDE%OISI1ý̙M Ѭ3~\Tfӎ&OA,wi᫇ b,p7lyx'sĴY5yV99capr q4?VAl8y1.>EkgZ,jX`IjY,,깳ĞVna~,Z@OLpc!`!`G6C0(tJ?df,-SYBȑƍq{.D%gΜ[#7q
)19YYjGo0:n={ j+oUr={% 8fEQC,.cǎ@N<2
V3
K&}͙&ꗔx^.
~(
{
QS믟W4a#w\\xȁ)AG/)V(_7!څƏ{1G$_1-Se?ǎE.~{%e,PhnGaH&YmVu7xg2HRU~}a3WHS'6jJᱣG3 &^ʖyYF'+;%pJm&`!`!pZkm!`@xE<{Z
8q66n>vl%_Ly_99XS;w
9#{Ŗ>ȢCߟY[nճ/%kVC`Ks*λ;zתeKR'
òe
Zr_ݾ];ʂ/Ç
cҥK#DxJIV&OFyfUV."NupM5"@$"@ш*g[:hH#G&ɌX2)svaϏD!q*G bY0W.E1uV 8xbg
?8l ˹xD#d4畗^妛(HǮB >bBt1<Ѥ DFX
]\oXq:,ɯ&PОq!MFWfA-ٓ6^r MQڳ4q^TYZoڪԓO2n؋{q:5d%SNζmk#uСG=O3`;ᮜ3{GH"F.q!`!`@!@:Ç/[l~`[zK1C }ۦb`0F'_W/|Xcpԍt^te䧟~ؐ͛zO<~ڼiS˖-/첋.tLֳgϞ9sf0C*cÍjպ\9Kl,$jW^)U믿.a5:|8FHp8I5mBB?,E|-֘v'1'3)QӨ@8[`*,7! T6c+Pym]FG
Ѓ
ڶuka*%?Ŋ%zb[05'XU5&"XԯO^Ae%HiWPp/DHSOE3eA?X>^>NL$*jǎ
Q(,HeGVIbz%K3B3ᅙ<4X|
h^
B͞5)}D?-of0ó'wƏ>=J)^'x ÄC#)$DoްHfG:|8v@Zl7 X5□1KgCrJ__0}d P$)8OKۆ!`!`G'?EPA,\04C0Wmz ̩'%KۗNq6Rv?2zg7(2pp%,^8pЧd,0ĒoՃ
j߾ڵA<ߺU+,-=FBg:uv
~B3ja^8O?
UbZ
PTa1jnV xtAg/1sZ'eO87fe s@fUVZqw%TO$ys֭a1}M`Yd!z;sLj<Yi:T+]N.8묳(!\5S
i/:84.͙CZB^3g$9ʔGxԇ-u|Y cbI'vFpp1qʛ'av[i=s2#2\xD@njxBANZ5ƥ%$Eyx'Nڿ*XV͐
XxHrh;,@ˑz5ma<-r)¼3SPW^I0;gh筟0P[ƛhQZ5jj
ưXGwYDxzi\A`d PpW?CQbx[eC0C`KOȑ#P%g~>N1۷/ɢܔ!v@ۊe7!TT"Ļ/\a/ fTATP"R(ʏG`ɉa$c)ipNඝ #W'qV=笳kXЀXzC