Vaccinia Protein F12 Has Structural Similarity to Kinesin Light Chain and Contains a Motor Binding Motif Required for Virion Export
Vaccinia virus (VACV) uses microtubules for export of virions to the cell surface and this process requires the viral protein F12. Here we show that F12 has structural similarity to kinesin light chain (KLC), a subunit of the kinesin-1 motor that binds cargo. F12 and KLC share similar size, pI, hydropathy and cargo-binding tetratricopeptide repeats (TPRs). Moreover, molecular modeling of F12 TPRs upon the crystal structure of KLC2 TPRs showed a striking conservation of structure. We also identified multiple TPRs in VACV proteins E2 and A36. Data presented demonstrate that F12 is critical for recruitment of kinesin-1 to virions and that a conserved tryptophan and aspartic acid (WD) motif, which is conserved in the kinesin-1-binding sequence (KBS) of the neuronal protein calsyntenin/alcadein and several other cellular kinesin-1 binding proteins, is essential for kinesin-1 recruitment and virion transport. In contrast, mutation of WD motifs in protein A36 revealed they were not required for kinesin-1 recruitment or IEV transport. This report of a viral KLC-like protein containing a KBS that is conserved in several cellular proteins advances our understanding of how VACV recruits the kinesin motor to virions, and exemplifies how viruses use molecular mimicry of cellular components to their advantage.
Vyšlo v časopise:
Vaccinia Protein F12 Has Structural Similarity to Kinesin Light Chain and Contains a Motor Binding Motif Required for Virion Export. PLoS Pathog 6(2): e32767. doi:10.1371/journal.ppat.1000785
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1000785
Souhrn
Vaccinia virus (VACV) uses microtubules for export of virions to the cell surface and this process requires the viral protein F12. Here we show that F12 has structural similarity to kinesin light chain (KLC), a subunit of the kinesin-1 motor that binds cargo. F12 and KLC share similar size, pI, hydropathy and cargo-binding tetratricopeptide repeats (TPRs). Moreover, molecular modeling of F12 TPRs upon the crystal structure of KLC2 TPRs showed a striking conservation of structure. We also identified multiple TPRs in VACV proteins E2 and A36. Data presented demonstrate that F12 is critical for recruitment of kinesin-1 to virions and that a conserved tryptophan and aspartic acid (WD) motif, which is conserved in the kinesin-1-binding sequence (KBS) of the neuronal protein calsyntenin/alcadein and several other cellular kinesin-1 binding proteins, is essential for kinesin-1 recruitment and virion transport. In contrast, mutation of WD motifs in protein A36 revealed they were not required for kinesin-1 recruitment or IEV transport. This report of a viral KLC-like protein containing a KBS that is conserved in several cellular proteins advances our understanding of how VACV recruits the kinesin motor to virions, and exemplifies how viruses use molecular mimicry of cellular components to their advantage.
Zdroje
1. MossB
2007
FieldsBN
KnipeDM
HowleyPM
Fields' virology Philadelphia Wolters Kluwer Health/Lippincott Williams & Wilkins 2 v. (xix, 3091, 3086 p.)
2. RobertsKL
SmithGL
2008 Vaccinia virus morphogenesis and dissemination. Trends Microbiol 16 472 479
3. SmithGL
VanderplasschenA
LawM
2002 The formation and function of extracellular enveloped vaccinia virus. J Gen Virol 83 2915 2931
4. DalesS
MosbachEH
1968 Vaccinia as a model for membrane biogenesis. Virology 35 564 583
5. ConditRC
MoussatcheN
TraktmanP
2006 In a nutshell: structure and assembly of the vaccinia virion. Adv Virus Res 66 31 124
6. SandersonCM
HollinsheadM
SmithGL
2000 The vaccinia virus A27L protein is needed for the microtubule-dependent transport of intracellular mature virus particles. J Gen Virol 81 47 58
7. WardBM
2005 Visualization and characterization of the intracellular movement of vaccinia virus intracellular mature virions. J Virol 79 4755 4763
8. IchihashiY
MatsumotoS
DalesS
1971 Biogenesis of poxviruses: role of A-type inclusions and host cell membranes in virus dissemination. Virology 46 507 532
9. PayneLG
KristensonK
1979 Mechanism of vaccinia virus release and its specific inhibition by N1-isonicotinoyl-N2-3-methyl-4-chlorobenzoylhydrazine. J Virol 32 614 622
10. MorganC
1976 Vaccinia virus reexamined: development and release. Virology 73 43 58
11. HillerG
WeberK
1985 Golgi-derived membranes that contain an acylated viral polypeptide are used for vaccinia virus envelopment. J Virol 55 651 659
12. ToozeJ
HollinsheadM
ReisB
RadsakK
KernH
1993 Progeny vaccinia and human cytomegalovirus particles utilize early endosomal cisternae for their envelopes. Eur J Cell Biol 60 163 178
13. SchmelzM
SodeikB
EricssonM
WolffeEJ
ShidaH
1994 Assembly of vaccinia virus: the second wrapping cisterna is derived from the trans Golgi network. J Virol 68 130 147
14. HollinsheadM
RodgerG
Van EijlH
LawM
HollinsheadR
2001 Vaccinia virus utilizes microtubules for movement to the cell surface. J Cell Biol 154 389 402
15. WardBM
MossB
2001 Vaccinia virus intracellular movement is associated with microtubules and independent of actin tails. J Virol 75 11651 11663
16. GeadaMM
GalindoI
LorenzoMM
PerdigueroB
BlascoR
2001 Movements of vaccinia virus intracellular enveloped virions with GFP tagged to the F13L envelope protein. J Gen Virol 82 2747 2760
17. RietdorfJ
PloubidouA
ReckmannI
HolmstromA
FrischknechtF
2001 Kinesin-dependent movement on microtubules precedes actin-based motility of vaccinia virus. Nat Cell Biol 3 992 1000
18. van EijlH
HollinsheadM
RodgerG
ZhangWH
SmithGL
2002 The vaccinia virus F12L protein is associated with intracellular enveloped virus particles and is required for their egress to the cell surface. J Gen Virol 83 195 207
19. Herrero-MartinezE
RobertsKL
HollinsheadM
SmithGL
2005 Vaccinia virus intracellular enveloped virions move to the cell periphery on microtubules in the absence of the A36R protein. J Gen Virol 86 2961 2968
20. ZhangWH
WilcockD
SmithGL
2000 Vaccinia virus F12L protein is required for actin tail formation, normal plaque size, and virulence. J Virol 74 11654 11662
21. WardBM
MossB
2004 Vaccinia virus A36R membrane protein provides a direct link between intracellular enveloped virions and the microtubule motor kinesin. J Virol 78 2486 2493
22. SchnappBJ
2003 Trafficking of signaling modules by kinesin motors. J Cell Sci 116 2125 2135
23. GaugerAK
GoldsteinLS
1993 The Drosophila kinesin light chain. Primary structure and interaction with kinesin heavy chain. J Biol Chem 268 13657 13666
24. AdioS
RethJ
BatheF
WoehlkeG
2006 Review: regulation mechanisms of Kinesin-1. J Muscle Res Cell Motil 27 153 160
25. HirokawaN
TakemuraR
2005 Molecular motors and mechanisms of directional transport in neurons. Nat Rev Neurosci 6 201 214
26. GindhartJGJr
GoldsteinLS
1996 Tetratrico peptide repeats are present in the kinesin light chain. Trends Biochem Sci 21 52 53
27. D'AndreaLD
ReganL
2003 TPR proteins: the versatile helix. Trends Biochem Sci 28 655 662
28. BowmanAB
KamalA
RitchingsBW
PhilpAV
McGrailM
2000 Kinesin-dependent axonal transport is mediated by the sunday driver (SYD) protein. Cell 103 583 594
29. BracaleA
CescaF
NeubrandVE
NewsomeTP
WayM
2007 Kidins220/ARMS is transported by a kinesin-1-based mechanism likely to be involved in neuronal differentiation. Mol Biol Cell 18 142 152
30. KonecnaA
FrischknechtR
KinterJ
LudwigA
SteubleM
2006 Calsyntenin-1 docks vesicular cargo to kinesin-1. Mol Biol Cell 17 3651 3663
31. KimuraT
WatanabeH
IwamatsuA
KaibuchiK
2005 Tubulin and CRMP-2 complex is transported via Kinesin-1. J Neurochem 93 1371 1382
32. McGuireJR
RongJ
LiSH
LiXJ
2006 Interaction of Huntingtin-associated protein-1 with kinesin light chain: implications in intracellular trafficking in neurons. J Biol Chem 281 3552 3559
33. KammC
BostonH
HewettJ
WilburJ
CoreyDP
2004 The early onset dystonia protein torsinA interacts with kinesin light chain 1. J Biol Chem 279 19882 19892
34. IchimuraT
Wakamiya-TsurutaA
ItagakiC
TaokaM
HayanoT
2002 Phosphorylation-dependent interaction of kinesin light chain 2 and the 14-3-3 protein. Biochemistry 41 5566 5572
35. KamalA
StokinGB
YangZ
XiaCH
GoldsteinLS
2000 Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron 28 449 459
36. AoyamaT
HataS
NakaoT
TanigawaY
OkaC
2009 Cayman ataxia protein caytaxin is transported by kinesin along neurites through binding to kinesin light chains. J Cell Sci 122 4177 4185
37. HenryT
CouillaultC
RockenfellerP
BoucrotE
DumontA
2006 The Salmonella effector protein PipB2 is a linker for kinesin-1. Proc Natl Acad Sci U S A 103 13497 13502
38. WozniakMJ
AllanVJ
2006 Cargo selection by specific kinesin light chain 1 isoforms. EMBO J 25 5457 5468
39. HammondJW
GriffinK
JihGT
StuckeyJ
VerheyKJ
2008 Co-operative versus independent transport of different cargoes by Kinesin-1. Traffic 9 725 741
40. MorfiniG
SzebenyiG
ElluruR
RatnerN
BradyST
2002 Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. Embo J 21 281 293
41. MorfiniG
SzebenyiG
BrownH
PantHC
PiginoG
2004 A novel CDK5-dependent pathway for regulating GSK3 activity and kinesin-driven motility in neurons. Embo J 23 2235 2245
42. NewsomeTP
ScaplehornN
WayM
2004 SRC mediates a switch from microtubule- to actin-based motility of vaccinia virus. Science 306 124 129
43. ArakawaY
CordeiroJV
SchleichS
NewsomeTP
WayM
2007 The release of vaccinia virus from infected cells requires RhoA-mDia modulation of cortical actin. Cell Host Microbe 1 227 240
44. FrischknechtF
MoreauV
RottgerS
GonfloniS
ReckmannI
1999 Actin-based motility of vaccinia virus mimics receptor tyrosine kinase signalling. Nature 401 926 929
45. ReevesPM
BommariusB
LebeisS
McNultyS
ChristensenJ
2005 Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases. Nat Med 11 731 739
46. MoreauV
FrischknechtF
ReckmannI
VincentelliR
RabutG
2000 A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization. Nat Cell Biol 2 441 448
47. ScaplehornN
HolmstromA
MoreauV
FrischknechtF
ReckmannI
2002 Grb2 and Nck act cooperatively to promote actin-based motility of vaccinia virus. Curr Biol 12 740 745
48. FrischknechtF
CudmoreS
MoreauV
ReckmannI
RottgerS
1999 Tyrosine phosphorylation is required for actin-based motility of vaccinia but not Listeria or Shigella. Curr Biol 9 89 92
49. WeisswangeI
NewsomeTP
SchleichS
WayM
2009 The rate of N-WASP exchange limits the extent of ARP2/3-complex-dependent actin-based motility. Nature 458 87 91
50. ParkinsonJE
SmithGL
1994 Vaccinia virus gene A36R encodes a M(r) 43–50 K protein on the surface of extracellular enveloped virus. Virology 204 376 390
51. SandersonCM
FrischknechtF
WayM
HollinsheadM
SmithGL
1998 Roles of vaccinia virus EEV-specific proteins in intracellular actin tail formation and low pH-induced cell-cell fusion. J Gen Virol 79(Pt 6) 1415 1425
52. WolffeEJ
WeisbergAS
MossB
1998 Role for the vaccinia virus A36R outer envelope protein in the formation of virus-tipped actin-containing microvilli and cell-to-cell virus spread. Virology 244 20 26
53. OgawaR
CalvertJG
YanagidaN
NazerianK
1993 Insertional inactivation of a fowlpox virus homologue of the vaccinia virus F12L gene inhibits the release of enveloped virions. J Gen Virol 74(Pt 1) 55 64
54. DomiA
WeisbergAS
MossB
2008 Vaccinia virus E2L null mutants exhibit a major reduction in extracellular virion formation and virus spread. J Virol 82 4215 4226
55. DoddingMP
NewsomeTP
CollinsonLM
EdwardsC
WayM
2009 An E2-F12 complex is required for IEV morphogenesis during vaccinia infection. Cell Microbiol
56. JohnstonSC
WardBM
2009 Vaccinia virus protein F12 associates with intracellular enveloped virions through an interaction with A36. J Virol 83 1708 1717
57. ChakrabartiS
SislerJR
MossB
1997 Compact, synthetic, vaccinia virus early/late promoter for protein expression. Biotechniques 23 1094 1097
58. LawM
HollinsheadM
LeeHJ
SmithGL
2004 Yaba-like disease virus protein Y144R, a member of the complement control protein family, is present on enveloped virions that are associated with virus-induced actin tails. J Gen Virol 85 1279 1290
59. CarterGC
LawM
HollinsheadM
SmithGL
2005 Entry of the vaccinia virus intracellular mature virion and its interactions with glycosaminoglycans. J Gen Virol 86 1279 1290
60. BradyST
PfisterKK
BloomGS
1990 A monoclonal antibody against kinesin inhibits both anterograde and retrograde fast axonal transport in squid axoplasm. Proc Natl Acad Sci U S A 87 1061 1065
61. CarterGC
RodgerG
MurphyBJ
LawM
KraussO
2003 Vaccinia virus cores are transported on microtubules. J Gen Virol 84 2443 2458
62. ArakiY
KawanoT
TaruH
SaitoY
WadaS
2007 The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport. Embo J 26 1475 1486
63. RossJL
AliMY
WarshawDM
2008 Cargo transport: molecular motors navigate a complex cytoskeleton. Curr Opin Cell Biol 20 41 47
64. HackneyDD
2007 Jump-starting kinesin. J Cell Biol 176 7 9
65. DaviesMV
Elroy-SteinO
JagusR
MossB
KaufmanRJ
1992 The vaccinia virus K3L gene product potentiates translation by inhibiting double-stranded-RNA-activated protein kinase and phosphorylation of the alpha subunit of eukaryotic initiation factor 2. J Virol 66 1943 1950
66. MooreJB
SmithGL
1992 Steroid hormone synthesis by a vaccinia enzyme: a new type of virus virulence factor. EMBO J 11 3490
67. AlcamiA
SmithGL
1992 A soluble receptor for interleukin-1 beta encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell 71 153 167
68. CoorayS
BaharMW
AbresciaNG
McVeyCE
BartlettNW
2007 Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein. J Gen Virol 88 1656 1666
69. ChenRA
RyzhakovG
CoorayS
RandowF
SmithGL
2008 Inhibition of IkappaB kinase by vaccinia virus virulence factor B14. PLoS Pathog 4 e22 doi:10.1371/journal.ppat.0040022
70. GrahamSC
BaharMW
CoorayS
ChenRA
WhalenDM
2008 Vaccinia virus proteins A52 and B14 Share a Bcl-2-like fold but have evolved to inhibit NF-kappaB rather than apoptosis. PLoS Pathog 4 e1000128 doi:10.1371/journal.ppat.1000128
71. CaiD
HoppeAD
SwansonJA
VerheyKJ
2007 Kinesin-1 structural organization and conformational changes revealed by FRET stoichiometry in live cells. J Cell Biol 176 51 63
72. van EijlH
HollinsheadM
SmithGL
2000 The vaccinia virus A36R protein is a type Ib membrane protein present on intracellular but not extracellular enveloped virus particles. Virology 271 26 36
73. StenoienDL
BradyST
1997 Immunochemical analysis of kinesin light chain function. Mol Biol Cell 8 675 689
74. AltschulSF
GishW
MillerW
MyersEW
LipmanDJ
1990 Basic local alignment search tool. J Mol Biol 215 403 410
75. JeanmouginF
ThompsonJD
GouyM
HigginsDG
GibsonTJ
1998 Multiple sequence alignment with Clustal X. Trends Biochem Sci 23 403 405
76. WaterhouseAM
ProcterJB
MartinDM
ClampM
BartonGJ
2009 Jalview Version 2–a multiple sequence alignment editor and analysis workbench. Bioinformatics 25 1189 1191
77. Marti-RenomMA
StuartAC
FiserA
SanchezR
MeloF
2000 Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct 29 291 325
78. LaskowskiRA
MossDS
ThorntonJM
1993 Main-chain bond lengths and bond angles in protein structures. J Mol Biol 231 1049 1067
79. VriendG
1990 WHAT IF: a molecular modeling and drug design program. J Mol Graph 8 52 56, 29
80. LuthyR
BowieJU
EisenbergD
1992 Assessment of protein models with three-dimensional profiles. Nature 356 83 85
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