#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

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

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#