%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Federico Rojas, Joanna Koszela, Jacqueline Búa, Briardo Llorente, Richard Burchmore, Manfred Auer, Jeremy C. Mottram, María Teresa Téllez-Iñón
The ubiquitin-conjugating enzyme CDC34 is essential for cytokinesis in contrast to putative subunits of a SCF complex in Trypanosoma brucei
www.plosntds.org
www.plosntds.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]
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005626.ref001)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005626.ref002)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005626.ref003)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005626.ref004)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005626.ref005)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005626.ref006)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005626.ref007)>>
endobj
23 0 obj
<>/Border[0 0 0]/A 24 0 R>>
endobj
24 0 obj
<>
endobj
15 0 obj
[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]
endobj
25 0 obj
<>stream
q
0.955 g
0 w
199.9998 707.4 m
575.9997 707.4 l
575.9997 494.4005 l
199.9998 494.4005 l
f*
0.83 0.64 0.02 0 k
232.7811 380.9197 m
237.5433 380.9197 l
h
f*
241.9654 380.9197 m
246.7276 380.9197 l
h
f*
537.2787 302.9102 m
541.9843 302.9102 l
h
f*
551.8488 263.9055 m
556.611 263.9055 l
h
f*
330.9165 224.9008 m
335.622 224.9008 l
h
f*
294.463 198.9354 m
299.1685 198.9354 l
h
f*
228.5858 146.948 m
233.2913 146.948 l
h
f*
0 g
1 j
1 J
11.9999 0 0 11.9999 209.9905 689.3858 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Author)Tj
3.137 0 Td
(summary)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 209.9905 671.4141 cm
BT
/F9 1 Tf
1 TL
-0.004 Tc
0 0 Td
(African)Tj
3.2314 0 Td
(sleeping)Tj
3.4639 0 Td
(sickness)Tj
3.4583 0 Td
(is)Tj
0.839 0 Td
(a)Tj
0.6463 0 Td
(neglected)Tj
3.9969 0 Td
(tropical)Tj
3.2768 0 Td
(disease)Tj
3.0104 0 Td
(caused)Tj
2.9083 0 Td
(by)Tj
1.1735 0 Td
(infection)Tj
3.7871 0 Td
(with)Tj
1.9899 0 Td
(the)Tj
1.4627 0 Td
(proto-)Tj
-33.2445 -1.3039 Td
(zoan)Tj
2.1259 0 Td
(parasite)Tj
/F14 1 Tf
3.3222 0 Td
[()75()-20()-13()4()16()6()7()-3()11( )6()]TJ
5.6182 0 Td
[(\n)11()-9()4()7(\r)2()]TJ
/F9 1 Tf
(,)Tj
2.8403 0 Td
(which)Tj
2.6532 0 Td
(is)Tj
0.8448 0 Td
(transmitted)Tj
4.8699 0 Td
(to)Tj
1.0261 0 Td
(humans)Tj
3.4356 0 Td
(by)Tj
1.1848 0 Td
(tsetse)Tj
2.3868 0 Td
(flies)Tj
1.8028 0 Td
(\()Tj
/F14 1 Tf
[()9()4()7()10()10()12()6()]TJ
/F9 1 Tf
-32.1106 -1.2982 Td
(genus\).)Tj
3.1124 0 Td
(Treatment)Tj
4.4503 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(disease)Tj
3.016 0 Td
(is)Tj
0.8504 0 Td
(complex)Tj
3.6227 0 Td
(and)Tj
1.7291 0 Td
(relies)Tj
2.313 0 Td
(on)Tj
1.2756 0 Td
(limited)Tj
3.0671 0 Td
(pharmaceutical)Tj
6.3666 0 Td
(options.)Tj
-32.2864 -1.2983 Td
(Understanding)Tj
6.2815 0 Td
(how)Tj
/F14 1 Tf
1.9389 0 Td
[()]TJ
/F9 1 Tf
(.)Tj
/F14 1 Tf
1.0318 0 Td
[(\n)11()-9()4()7(\r)2()]TJ
/F9 1 Tf
2.6135 0 Td
(regulates)Tj
3.7757 0 Td
(cell)Tj
1.5591 0 Td
(cycle)Tj
2.1883 0 Td
(progression)Tj
4.9209 0 Td
(at)Tj
0.9525 0 Td
(a)Tj
0.6519 0 Td
(molecular)Tj
4.2236 0 Td
(level)Tj
2.0126 0 Td
(when)Tj
-32.1503 -1.2983 Td
(alternating)Tj
4.558 0 Td
(between)Tj
3.5263 0 Td
(the)Tj
1.4683 0 Td
(mammalian)Tj
5.0457 0 Td
(host)Tj
1.9105 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4684 0 Td
(insect)Tj
2.5398 0 Td
(vector)Tj
2.6985 0 Td
(could)Tj
2.4548 0 Td
(lead)Tj
1.8482 0 Td
(to)Tj
1.0261 0 Td
(better)Tj
2.5399 0 Td
(thera-)Tj
-32.8193 -1.3039 Td
(pies.)Tj
2.0069 0 Td
(In)Tj
1.0998 0 Td
(this)Tj
1.6611 0 Td
(study,)Tj
2.6079 0 Td
(we)Tj
1.3152 0 Td
(examined)Tj
4.1216 0 Td
(different)Tj
/F14 1 Tf
3.6453 0 Td
[()]TJ
/F9 1 Tf
(.)Tj
/F14 1 Tf
1.0261 0 Td
[(\n)11()-9()4()7(\r)2()]TJ
/F9 1 Tf
2.6079 0 Td
(proteins)Tj
3.5036 0 Td
(with)Tj
1.9842 0 Td
(homology)Tj
4.2463 0 Td
(to)Tj
1.0148 0 Td
(components)Tj
-30.8407 -1.2982 Td
(of)Tj
1.0147 0 Td
(the)Tj
1.4684 0 Td
(SKP1-CUL1-F-box)Tj
7.8802 0 Td
(ubiquitin)Tj
3.9345 0 Td
(ligase)Tj
2.4151 0 Td
(complex)Tj
3.6227 0 Td
(\(SCFC\),)Tj
3.4582 0 Td
(previously)Tj
4.3483 0 Td
(characterized)Tj
5.5616 0 Td
(in)Tj
-33.7037 -1.2983 Td
(other)Tj
2.347 0 Td
(eukaryotes)Tj
4.5184 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(regulator)Tj
3.8664 0 Td
(of)Tj
1.0148 0 Td
(cell)Tj
1.5591 0 Td
(cycle)Tj
2.194 0 Td
(progression.)Tj
5.142 0 Td
(We)Tj
1.61 0 Td
(found)Tj
2.6192 0 Td
(that)Tj
1.7802 0 Td
(depletion)Tj
3.9798 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-33.3125 -1.3039 Td
(homologues)Tj
5.1136 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(putative)Tj
3.4412 0 Td
(SCFC)Tj
2.5512 0 Td
(cause)Tj
/F14 1 Tf
2.3867 0 Td
[()]TJ
/F9 1 Tf
(.)Tj
/F14 1 Tf
1.0375 0 Td
[(\n)11()-9()4()7(\r)2()]TJ
/F9 1 Tf
2.6135 0 Td
(to)Tj
1.0262 0 Td
(develop)Tj
3.3222 0 Td
(abnormally,)Tj
5.0116 0 Td
(generating)Tj
4.4674 0 Td
(differ-)Tj
-32.6379 -1.2983 Td
(ent)Tj
1.491 0 Td
(phenotypes)Tj
4.8018 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(mammalian)Tj
5.0399 0 Td
(and)Tj
1.7291 0 Td
(insect)Tj
2.5455 0 Td
(stages.)Tj
2.7893 0 Td
(Interestingly,)Tj
5.4879 0 Td
(depletion)Tj
3.9798 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(ubiqui-)Tj
-32.8363 -1.2983 Td
(tin)Tj
1.3322 0 Td
(conjugating)Tj
4.9663 0 Td
(enzyme)Tj
3.2995 0 Td
(TbCDC34)Tj
4.354 0 Td
(arrest)Tj
2.4775 0 Td
(cells)Tj
1.9218 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.652 0 Td
(pre-cytokinesis)Tj
6.2928 0 Td
(stage,)Tj
2.4265 0 Td
(indicating)Tj
4.2689 0 Td
(that)Tj
-33.029 -1.3039 Td
(this)Tj
1.6724 0 Td
(protein)Tj
3.1578 0 Td
(is)Tj
0.8447 0 Td
(essential)Tj
3.5829 0 Td
(for)Tj
1.389 0 Td
(cytokinesis.)Tj
4.8529 0 Td
(In)Tj
1.1055 0 Td
(addition)Tj
3.6 0 Td
(to)Tj
1.0261 0 Td
(improving)Tj
4.439 0 Td
(our)Tj
1.6214 0 Td
(fundamental)Tj
5.3178 0 Td
(under-)Tj
-32.6095 -1.2982 Td
(standing)Tj
3.6736 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(molecular)Tj
4.2179 0 Td
(regulation)Tj
4.3086 0 Td
(underlying)Tj
4.6035 0 Td
(the)Tj
1.4683 0 Td
(sophisticated)Tj
5.4311 0 Td
(life)Tj
1.4457 0 Td
(cycle)Tj
2.194 0 Td
(of)Tj
/F14 1 Tf
1.0148 0 Td
[()]TJ
/F9 1 Tf
(.)Tj
/F14 1 Tf
1.0318 0 Td
[(\n)11()-9()4()7(\r)2()]TJ
/F9 1 Tf
(,)Tj
-31.8725 -1.2983 Td
(this)Tj
1.6724 0 Td
(work)Tj
2.279 0 Td
(pinpoints)Tj
4.0535 0 Td
(a)Tj
0.6577 0 Td
(potential)Tj
3.7587 0 Td
(target)Tj
2.5115 0 Td
(for)Tj
1.3833 0 Td
(drug)Tj
2.1146 0 Td
(development)Tj
5.4085 0 Td
(against)Tj
3.0274 0 Td
(trypanosomiasis.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 450.9921 cm
BT
/F3 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 433.9842 cm
BT
/F9 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Transition)Tj
4.4333 0 Td
(from)Tj
2.2053 0 Td
(one)Tj
1.7008 0 Td
(cell)Tj
1.5591 0 Td
(cycle)Tj
2.1883 0 Td
(stage)Tj
2.2053 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(next)Tj
1.9559 0 Td
(is)Tj
0.8447 0 Td
(achieved)Tj
3.7021 0 Td
(in)Tj
1.0374 0 Td
(eukaryotes)Tj
4.5184 0 Td
(through)Tj
3.4413 0 Td
(mechanisms)Tj
-32.2864 -1.2982 Td
(that)Tj
1.7744 0 Td
(provide)Tj
3.2939 0 Td
(an)Tj
1.2018 0 Td
(all-or-none)Tj
4.7509 0 Td
(cyclin-dependent)Tj
7.1716 0 Td
(kinases)Tj
3.1124 0 Td
(\(CDKs\))Tj
3.3335 0 Td
(activation.)Tj
4.3824 0 Td
(The)Tj
1.7801 0 Td
(activity)Tj
3.1181 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
-34.9339 -1.2983 Td
(enzymes)Tj
3.6623 0 Td
(is)Tj
0.8504 0 Td
(regulated)Tj
3.9344 0 Td
(by)Tj
1.1849 0 Td
(several)Tj
2.931 0 Td
(mechanisms,)Tj
5.4312 0 Td
(including)Tj
4.0421 0 Td
(association)Tj
4.6262 0 Td
(with)Tj
2.0012 0 Td
(regulatory)Tj
4.32 0 Td
(subunits)Tj
-32.9837 -1.3039 Td
(\(cyclins\),)Tj
3.8494 0 Td
(phosphorylation)Tj
6.8088 0 Td
(and)Tj
1.7347 0 Td
(dephosphorylation)Tj
7.7613 0 Td
(and)Tj
1.7291 0 Td
(interaction)Tj
4.6091 0 Td
(with)Tj
1.9956 0 Td
(CDK)Tj
2.296 0 Td
(inhibitors)Tj
-30.784 -1.2983 Td
(\(CKIs\))Tj
2.9366 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(2)Tj
0 g
(].)Tj
1.2642 0 Td
(Levels)Tj
2.6646 0 Td
(of)Tj
1.0148 0 Td
(cyclins)Tj
2.948 0 Td
(\(CYC\),)Tj
3.0841 0 Td
(CKIs)Tj
2.2563 0 Td
(and)Tj
1.7292 0 Td
(many)Tj
2.4774 0 Td
(other)Tj
2.3471 0 Td
(cell)Tj
1.559 0 Td
(cycle)Tj
2.194 0 Td
(regulators)Tj
4.2236 0 Td
(oscillate)Tj
3.4299 0 Td
(dur-)Tj
-35.3874 -1.2982 Td
(ing)Tj
1.5023 0 Td
(the)Tj
1.4683 0 Td
(cell)Tj
1.5591 0 Td
(cycle)Tj
2.1883 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(result)Tj
2.4492 0 Td
(of)Tj
1.0148 0 Td
(periodic)Tj
3.5206 0 Td
(proteolysis,)Tj
4.7621 0 Td
(generating)Tj
4.4618 0 Td
(a)Tj
0.6576 0 Td
(unidirectional)Tj
5.879 0 Td
(control.)Tj
3.3449 0 Td
(These)Tj
-34.4804 -1.3039 Td
(proteins)Tj
3.5149 0 Td
(are)Tj
1.4456 0 Td
(targeted)Tj
3.464 0 Td
(for)Tj
1.3833 0 Td
(degradation)Tj
5.0286 0 Td
(by)Tj
1.1792 0 Td
(polyubiquitination,)Tj
7.9426 0 Td
(i.e.)Tj
1.3606 0 Td
(the)Tj
1.4684 0 Td
(attachment)Tj
4.7281 0 Td
(of)Tj
1.0148 0 Td
(multiple)Tj
-32.5301 -1.2983 Td
(copies)Tj
2.7155 0 Td
(of)Tj
1.0148 0 Td
(ubiquitin.)Tj
4.1669 0 Td
(This)Tj
1.9843 0 Td
(process)Tj
3.1861 0 Td
(is)Tj
0.8447 0 Td
(initiated)Tj
3.5546 0 Td
(by)Tj
1.1792 0 Td
(an)Tj
1.2076 0 Td
(ubiquitin-activating)Tj
8.175 0 Td
(enzyme)Tj
3.3052 0 Td
(\(E1\),)Tj
2.1714 0 Td
(which)Tj
-33.5053 -1.2983 Td
(then)Tj
2.0182 0 Td
(transfers)Tj
3.6737 0 Td
(ubiquitin)Tj
3.9401 0 Td
(to)Tj
1.0262 0 Td
(an)Tj
1.2018 0 Td
(active)Tj
2.5229 0 Td
(cysteine)Tj
3.4185 0 Td
(residue)Tj
3.1238 0 Td
(of)Tj
1.0148 0 Td
(an)Tj
1.2019 0 Td
(ubiquitin-conjugating)Tj
9.0254 0 Td
(enzyme)Tj
3.3052 0 Td
(\(E2\))Tj
-35.4725 -1.2982 Td
(as)Tj
1.0147 0 Td
(a)Tj
0.652 0 Td
(thioester)Tj
3.6964 0 Td
(linkage.)Tj
3.3278 0 Td
(Although)Tj
4.0025 0 Td
(E2s)Tj
1.6271 0 Td
(can)Tj
1.6271 0 Td
(attach)Tj
2.6362 0 Td
(ubiquitin)Tj
3.9344 0 Td
(directly)Tj
3.2372 0 Td
(to)Tj
1.0261 0 Td
(a)Tj
0.652 0 Td
(lysine)Tj
2.5228 0 Td
(residue)Tj
3.1181 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.6519 0 Td
(sub-)Tj
-34.7638 -1.304 Td
(strate,)Tj
2.6305 0 Td
(most)Tj
2.2053 0 Td
(physiological)Tj
5.4425 0 Td
(ubiquitination)Tj
5.9924 0 Td
(reactions)Tj
3.8551 0 Td
(require)Tj
3.1124 0 Td
(an)Tj
1.2019 0 Td
(ubiquitin)Tj
3.9401 0 Td
(ligase,)Tj
2.6419 0 Td
(or)Tj
1.0942 0 Td
(E3)Tj
1.2699 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(].)Tj
1.5987 0 Td
(Once)Tj
-34.9849 -1.2982 Td
(the)Tj
1.4683 0 Td
(substrate)Tj
3.8041 0 Td
(is)Tj
0.8447 0 Td
(polyubiquitinated)Tj
7.3473 0 Td
(by)Tj
1.1792 0 Td
(an)Tj
1.2076 0 Td
(E3,)Tj
1.4853 0 Td
(it)Tj
0.7881 0 Td
(is)Tj
0.8503 0 Td
(then)Tj
2.0183 0 Td
(recognized)Tj
4.5864 0 Td
(and)Tj
1.7348 0 Td
(degraded)Tj
3.9175 0 Td
(by)Tj
1.1849 0 Td
(the)Tj
1.4683 0 Td
(26S)Tj
1.6441 0 Td
(pro-)Tj
-35.5292 -1.2983 Td
(teasome.)Tj
3.7133 0 Td
(The)Tj
1.7802 0 Td
(specificity)Tj
4.2122 0 Td
(of)Tj
1.0148 0 Td
(ubiquitin-dependent)Tj
8.5266 0 Td
(proteolysis)Tj
4.5354 0 Td
(derives)Tj
3.0444 0 Td
(from)Tj
2.211 0 Td
(the)Tj
1.4683 0 Td
(many)Tj
2.4775 0 Td
(hundreds)Tj
-32.9837 -1.3039 Td
(of)Tj
1.0147 0 Td
(E3)Tj
1.2643 0 Td
(ubiquitin)Tj
3.9345 0 Td
(ligases)Tj
2.7779 0 Td
(that)Tj
1.7801 0 Td
(recognize)Tj
4.0649 0 Td
(particular)Tj
4.1102 0 Td
(substrates)Tj
4.1612 0 Td
(through)Tj
3.4469 0 Td
(interaction)Tj
4.6091 0 Td
(domains)Tj
3.6794 0 Td
([)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(].)Tj
-33.647 -1.2983 Td
(Two)Tj
-0.01 Tc
2.0239 0 Td
(E3)Tj
1.2529 0 Td
(enzymes)Tj
3.6226 0 Td
(that)Tj
1.7575 0 Td
(comprise)Tj
3.8608 0 Td
(multiprotein)Tj
5.2384 0 Td
(components)Tj
5.1136 0 Td
(are)Tj
1.4344 0 Td
(of)Tj
1.0034 0 Td
(particular)Tj
4.0479 0 Td
(importance)Tj
4.7735 0 Td
(for)Tj
-35.3251 -1.2982 Td
(cell)Tj
1.5306 0 Td
(cycle)Tj
2.1544 0 Td
(progression:)Tj
5.0683 0 Td
(the)Tj
1.4456 0 Td
(SKP1-CULLIN1-F-box)Tj
9.377 0 Td
(complex)Tj
3.5773 0 Td
(\(SCFC\))Tj
3.1861 0 Td
(and)Tj
1.7065 0 Td
(the)Tj
1.4513 0 Td
(anaphase)Tj
3.8437 0 Td
(promoting)Tj
-33.3408 -1.3039 Td
(complex)Tj
3.5773 0 Td
(or)Tj
1.0884 0 Td
(cyclosome)Tj
4.3314 0 Td
(\(APC/C\))Tj
3.7587 0 Td
([)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(].)Tj
1.576 0 Td
(The)Tj
1.7632 0 Td
(SCFC)Tj
2.5285 0 Td
(consists)Tj
3.2995 0 Td
(of)Tj
1.0034 0 Td
(three)Tj
2.2337 0 Td
(invariant)Tj
3.7871 0 Td
(components)Tj
5.1193 0 Td
(includ-)Tj
-34.0665 -1.2983 Td
(ing)Tj
1.4796 0 Td
(SKP1,)Tj
2.6022 0 Td
(CULLIN1,)Tj
4.422 0 Td
(RBX1/ROC1/HRT1,)Tj
8.3282 0 Td
(the)Tj
1.457 0 Td
(E2)Tj
1.2529 0 Td
(ubiquitin)Tj
3.8834 0 Td
(conjugating)Tj
4.8926 0 Td
(enzyme)Tj
3.2655 0 Td
(CDC34)Tj
3.2088 0 Td
(and)Tj
-34.7922 -1.2983 Td
(various)Tj
3.101 0 Td
(F-box)Tj
2.5455 0 Td
(proteins)Tj
3.4639 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
1.5818 0 Td
(SKP1)Tj
2.3754 0 Td
(and)Tj
1.7178 0 Td
(CULLIN1)Tj
4.2009 0 Td
(are)Tj
1.4343 0 Td
(required)Tj
3.5886 0 Td
(for)Tj
1.372 0 Td
(the)Tj
1.4513 0 Td
(structural)Tj
4.0195 0 Td
(organization)Tj
5.2101 0 Td
(of)Tj
-36.0621 -1.3039 Td
(the)Tj
1.4513 0 Td
(SCFC,)Tj
2.7439 0 Td
(whereas)Tj
3.4016 0 Td
(RBX1)Tj
2.5284 0 Td
(is)Tj
0.8334 0 Td
(a)Tj
0.652 0 Td
(RING)Tj
2.6078 0 Td
(\(Really)Tj
2.9424 0 Td
(Interesting)Tj
4.5014 0 Td
(New)Tj
2.0466 0 Td
(Gene\)-finger)Tj
5.3121 0 Td
(protein)Tj
3.1124 0 Td
(that)Tj
1.7518 0 Td
(interacts)Tj
-33.8851 -1.2983 Td
(with)Tj
1.9729 0 Td
(E2-ubiquitin-conjugating)Tj
10.2783 0 Td
(enzymes.)Tj
3.8438 0 Td
(F-box)Tj
2.5455 0 Td
(proteins)Tj
3.4695 0 Td
(play)Tj
1.8482 0 Td
(a)Tj
0.6463 0 Td
(unique)Tj
2.9877 0 Td
(role)Tj
1.7405 0 Td
(in)Tj
1.0261 0 Td
(SCFC)Tj
2.5285 0 Td
(function,)Tj
3.7984 0 Td
(as)Tj
-36.6857 -1.2982 Td
(they)Tj
1.8992 0 Td
(interact)Tj
3.2371 0 Td
(with)Tj
1.9729 0 Td
(SKP1)Tj
2.3811 0 Td
(via)Tj
1.3549 0 Td
(their)Tj
2.0807 0 Td
(F-box)Tj
2.5454 0 Td
(motif)Tj
2.3698 0 Td
(and)Tj
1.7121 0 Td
(simultaneously)Tj
6.1625 0 Td
(bind)Tj
2.0466 0 Td
(specific)Tj
3.1408 0 Td
(substrates)Tj
4.1045 0 Td
(to)Tj
1.0148 0 Td
(the)Tj
-36.0224 -1.2983 Td
(SCFC)Tj
2.5228 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
1.5817 0 Td
(Each)Tj
2.1486 0 Td
(F-box)Tj
2.5455 0 Td
(is)Tj
0.8391 0 Td
(responsible)Tj
4.6885 0 Td
(for)Tj
1.3662 0 Td
(recruiting)Tj
4.1216 0 Td
(individual)Tj
4.2293 0 Td
(hyperphosphorylated)Tj
8.6229 0 Td
(substrates)Tj
-32.6662 -1.3039 Td
(to)Tj
1.0147 0 Td
(various)Tj
3.0955 0 Td
(SCFCs)Tj
2.8856 0 Td
(that)Tj
1.7518 0 Td
(differ)Tj
2.3528 0 Td
(in)Tj
1.0204 0 Td
(their)Tj
2.0806 0 Td
(F-box)Tj
2.5455 0 Td
(adapter)Tj
3.1862 0 Td
(protein.)Tj
3.3278 0 Td
(Once)Tj
2.3414 0 Td
(the)Tj
1.4513 0 Td
(substrate)Tj
3.7474 0 Td
(is)Tj
0.8334 0 Td
(recruited,)Tj
-31.6344 -1.2983 Td
(CDC34)Tj
3.2031 0 Td
(transfers)Tj
3.6226 0 Td
(ubiquitin)Tj
3.8835 0 Td
(molecules)Tj
4.1442 0 Td
(onto)Tj
2.0579 0 Td
(lysine)Tj
2.4832 0 Td
(residues)Tj
3.4355 0 Td
(in)Tj
1.0262 0 Td
(the)Tj
1.4513 0 Td
(substrate,)Tj
3.9685 0 Td
(building)Tj
3.5263 0 Td
(polyubiqui-)Tj
-32.8023 -1.2982 Td
(tin)Tj
1.3152 0 Td
(chains.)Tj
2.965 0 Td
(Polyubiquitinated)Tj
7.285 0 Td
(proteins)Tj
3.4696 0 Td
(are)Tj
1.4287 0 Td
(recognised)Tj
4.4787 0 Td
(and)Tj
1.7121 0 Td
(degraded)Tj
3.8721 0 Td
(by)Tj
1.1679 0 Td
(the)Tj
1.457 0 Td
(26)Tj
/F14 1 Tf
[()]TJ
/F9 1 Tf
1.6044 0 Td
(proteasome.)Tj
-0.004 Tc
-29.5595 -1.304 Td
(The)Tj
1.7858 0 Td
(protozoan)Tj
4.32 0 Td
(parasite)Tj
/F14 1 Tf
3.3278 0 Td
[()75()-20()-13()4()16()6()7()-3()11( )6()]TJ
5.6182 0 Td
[(\n)11()-9()4()7(\r)2()]TJ
/F9 1 Tf
2.6192 0 Td
(is)Tj
0.8448 0 Td
(the)Tj
1.4683 0 Td
(etiological)Tj
4.3086 0 Td
(agent)Tj
2.3868 0 Td
(of)Tj
1.0148 0 Td
(African)Tj
3.2371 0 Td
(trypanosomi-)Tj
-32.1276 -1.2982 Td
(asis)Tj
1.644 0 Td
(in)Tj
1.0318 0 Td
(humans)Tj
3.4413 0 Td
(\(sleeping)Tj
3.8097 0 Td
(sickness\))Tj
3.8041 0 Td
(and)Tj
1.7291 0 Td
(cattle)Tj
2.3471 0 Td
(\(nagana\).)Tj
3.9855 0 Td
(This)Tj
1.9899 0 Td
(parasite)Tj
3.3278 0 Td
(has)Tj
1.5421 0 Td
(a)Tj
0.6519 0 Td
(complex)Tj
3.6227 0 Td
(life)Tj
1.4456 0 Td
(cycle)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 183.2882 23.6976 re
W* n
q
183.2315 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 408.1322 745.7952 cm
BT
/F8 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Trypanoso)Tj
4.6488 0 Td
(ma)Tj
1.5945 0 Td
(brucei)Tj
/F0 1 Tf
2.8914 0 Td
(ubiquit)Tj
2.8772 0 Td
(ination)Tj
3.1039 0 Td
(complex)Tj
3.8835 0 Td
(SCF)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
163.5591 34.9228 m
317.7071 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
(Neglected)Tj
4.6417 0 Td
(Tropical)Tj
3.7135 0 Td
(Disease)Tj
3.5433 0 Td
(s)Tj
0.7158 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8197 0 Td
(1/journal.pn)Tj
5.1237 0 Td
(td.00056)Tj
3.8197 0 Td
(26)Tj
0 g
2.0905 0 Td
(June)Tj
2.3528 0 Td
(13,)Tj
1.5874 0 Td
(2017)Tj
24.9876 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(22)Tj
/F11 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(received)Tj
3.3023 0 Td
(from)Tj
2.0056 0 Td
(Boehringer-Inge)Tj
6.0024 0 Td
(lheim)Tj
2.2535 0 Td
(research)Tj
-13.5638 -1.3748 Td
(fellowship)Tj
3.7346 0 Td
(.)Tj
0.4465 0 Td
(The)Tj
1.5874 0 Td
(Wellcome)Tj
3.9048 0 Td
(Trust)Tj
2.1472 0 Td
(Centre)Tj
2.6292 0 Td
(for)Tj
-14.4497 -1.3749 Td
(Molecular)Tj
3.8764 0 Td
(Parasitology)Tj
4.8047 0 Td
(is)Tj
0.8292 0 Td
(supported)Tj
3.9968 0 Td
(by)Tj
1.1127 0 Td
(core)Tj
-14.6198 -1.3748 Td
(funding)Tj
3.033 0 Td
(from)Tj
2.0127 0 Td
(the)Tj
1.3677 0 Td
(Wellcome)Tj
3.9047 0 Td
(Trust)Tj
2.1544 0 Td
([104111])Tj
3.4512 0 Td
(.)Tj
0.4465 0 Td
(The)Tj
-16.3702 -1.3748 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 -1.3748 Td
(the)Tj
1.3677 0 Td
(manuscript.)Tj
/F10 1 Tf
-1.3677 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F11 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
26 0 obj
<>stream
endstream
endobj
27 0 obj
<>stream
endstream
endobj
28 0 obj
<>stream
endstream
endobj
29 0 obj
<>stream
endstream
endobj
30 0 obj
<>stream
endstream
endobj
31 0 obj
<>stream
endstream
endobj
32 0 obj
<>stream
endstream
endobj
33 0 obj
<>stream
BT
10.3394 72.3407 Td
(exist.)Tj
ET
Q
endstream
endobj
34 0 obj
<>/ColorSpace<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 38 0 R/Contents 39 0 R/TrimBox[0 0 612 792]>>
endobj
37 0 obj
[/ICCBased 40 0 R]
endobj
40 0 obj
<>stream
xwTSϽ7PkhRH
H.*1 J "6DTpDQ2(C"QDqpIdy͛~kg}ֺ LX Xňg` l pBF|،l *? Y"1 P\8=W%Oɘ4M0J"Y2Vs,[|e92<se'9`2&ctI@o|N6 (.sSdl-c(2-y H_/XZ.$&\SM07#1ؙYr fYym";8980m-m(]v^DW~
emi ]P`/ u}q|^R,g+\Kk)/C_|Rax8t1C^7nfzDp柇u$/ED˦L L[B@ٹЖX!@~ (* {d+}G͋љς}WL$cGD2QZ4 E@@ A(q`1D `'u46ptc48.`R0)
@Rt CXCP%CBH@Rf[(t
CQhz#0 Zl`O828.p|O×X
?:0FBx$ !i@ڐH[EE1PL⢖V6QP>U(j
MFk t,:.FW8c1L&ӎ9ƌaX:
rbl1
{{{;}#tp8_\8"Ey.,X%%Gщ1-9ҀKl.oo/O$&'=JvMޞ