#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The N-Terminal Domain of the Arenavirus L Protein Is an RNA Endonuclease Essential in mRNA Transcription


Arenaviridae synthesize viral mRNAs using short capped primers presumably acquired from cellular transcripts by a ‘cap-snatching’ mechanism. Here, we report the crystal structure and functional characterization of the N-terminal 196 residues (NL1) of the L protein from the prototypic arenavirus: lymphocytic choriomeningitis virus. The NL1 domain is able to bind and cleave RNA. The 2.13 Å resolution crystal structure of NL1 reveals a type II endonuclease α/β architecture similar to the N-terminal end of the influenza virus PA protein. Superimposition of both structures, mutagenesis and reverse genetics studies reveal a unique spatial arrangement of key active site residues related to the PD…(D/E)XK type II endonuclease signature sequence. We show that this endonuclease domain is conserved and active across the virus families Arenaviridae, Bunyaviridae and Orthomyxoviridae and propose that the arenavirus NL1 domain is the Arenaviridae cap-snatching endonuclease.


Vyšlo v časopise: The N-Terminal Domain of the Arenavirus L Protein Is an RNA Endonuclease Essential in mRNA Transcription. PLoS Pathog 6(9): e32767. doi:10.1371/journal.ppat.1001038
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001038

Souhrn

Arenaviridae synthesize viral mRNAs using short capped primers presumably acquired from cellular transcripts by a ‘cap-snatching’ mechanism. Here, we report the crystal structure and functional characterization of the N-terminal 196 residues (NL1) of the L protein from the prototypic arenavirus: lymphocytic choriomeningitis virus. The NL1 domain is able to bind and cleave RNA. The 2.13 Å resolution crystal structure of NL1 reveals a type II endonuclease α/β architecture similar to the N-terminal end of the influenza virus PA protein. Superimposition of both structures, mutagenesis and reverse genetics studies reveal a unique spatial arrangement of key active site residues related to the PD…(D/E)XK type II endonuclease signature sequence. We show that this endonuclease domain is conserved and active across the virus families Arenaviridae, Bunyaviridae and Orthomyxoviridae and propose that the arenavirus NL1 domain is the Arenaviridae cap-snatching endonuclease.


Zdroje

1. BrieseT

PaweskaJT

McMullanLK

HutchisonSK

StreetC

2009 Genetic detection and characterization of Lujo virus, a new hemorrhagic fever-associated arenavirus from southern Africa. PLoS Pathog 5 e1000455

2. CharrelRN

de LamballerieX

EmonetS

2008 Phylogeny of the genus Arenavirus. Curr Opin Microbiol 11 362 368

3. BartonLL

BuddSC

MorfittWS

PetersCJ

KsiazekTG

1993 Congenital lymphocytic choriomeningitis virus infection in twins. Pediatr Infect Dis J 12 942 946

4. BartonLL

HyndmanNJ

2000 Lymphocytic choriomeningitis virus: reemerging central nervous system pathogen. Pediatrics 105 E35

5. FischerSA

GrahamMB

KuehnertMJ

KottonCN

SrinivasanA

2006 Transmission of lymphocytic choriomeningitis virus by organ transplantation. N Engl J Med 354 2235 2249

6. PalaciosG

DruceJ

DuL

TranT

BirchC

2008 A new arenavirus in a cluster of fatal transplant-associated diseases. N Engl J Med 358 991 998

7. MeyerBJ

de la TorreJC

SouthernPJ

2002 Arenaviruses: genomic RNAs, transcription, and replication. Curr Top Microbiol Immunol 262 139 157

8. SalvatoMS

ShimomayeEM

1989 The completed sequence of lymphocytic choriomeningitis virus reveals a unique RNA structure and a gene for a zinc finger protein. Virology 173 1 10

9. MeyerBJ

SouthernPJ

1993 Concurrent sequence analysis of 5′ and 3′ RNA termini by intramolecular circularization reveals 5′ nontemplated bases and 3′ terminal heterogeneity for lymphocytic choriomeningitis virus mRNAs. J Virol 67 2621 2627

10. RajuR

RajuL

HackerD

GarcinD

CompansR

1990 Nontemplated bases at the 5′ ends of Tacaribe virus mRNAs. Virology 174 53 59

11. PolyakSJ

ZhengS

HarnishDG

1995 5′ termini of Pichinde arenavirus S RNAs and mRNAs contain nontemplated nucleotides. J Virol 69 3211 3215

12. PlotchSJ

BouloyM

KrugRM

1979 Transfer of 5′-terminal cap of globin mRNA to influenza viral complementary RNA during transcription in vitro. Proc Natl Acad Sci U S A 76 1618 1622

13. PlotchSJ

BouloyM

UlmanenI

KrugRM

1981 A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell 23 847 858

14. BishopDH

GayME

MatsuokoY

1983 Nonviral heterogeneous sequences are present at the 5′ ends of one species of snowshoe hare bunyavirus S complementary RNA. Nucleic Acids Res 11 6409 6418

15. DiasA

BouvierD

CrepinT

McCarthyAA

HartDJ

2009 The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 458 914 918

16. YuanP

BartlamM

LouZ

ChenS

ZhouJ

2009 Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Nature 458 909 913

17. LopezN

JacamoR

Franze-FernandezMT

2001 Transcription and RNA replication of tacaribe virus genome and antigenome analogs require N and L proteins: Z protein is an inhibitor of these processes. J Virol 75 12241 12251

18. MullerR

PochO

DelarueM

BishopDH

BouloyM

1994 Rift Valley fever virus L segment: correction of the sequence and possible functional role of newly identified regions conserved in RNA-dependent polymerases. J Gen Virol 75 Pt 6 1345 1352

19. ViethS

TordaAE

AsperM

SchmitzH

GuntherS

2004 Sequence analysis of L RNA of Lassa virus. Virology 318 153 168

20. LukashevichIS

DjavaniM

ShapiroK

SanchezA

RavkovE

1997 The Lassa fever virus L gene: nucleotide sequence, comparison, and precipitation of a predicted 250 kDa protein with monospecific antiserum. J Gen Virol 78 Pt 3 547 551

21. WildaM

LopezN

CasabonaJC

Franze-FernandezMT

2008 Mapping of the tacaribe arenavirus Z-protein binding sites on the L protein identified both amino acids within the putative polymerase domain and a region at the N terminus of L that are critically involved in binding. J Virol 82 11454 11460

22. HolmL

KaariainenS

RosenstromP

SchenkelA

2008 Searching protein structure databases with DaliLite v.3. Bioinformatics 24 2780 2781

23. NicholSTBBJ

ElliottRM

2005 Virus Taxonomy, VIIIth Report of the ICTV. Fauquet CM, Mayo AM, Maniloff J et al eds London: Elsevier Academic Press 695 716

24. GroMC

Di BonitoP

AccardiL

GiorgiC

1992 Analysis of 3′ and 5′ ends of N and NSs messenger RNAs of Toscana Phlebovirus. Virology 191 435 438

25. Frias-StaheliN

GiannakopoulosNV

KikkertM

TaylorSL

BridgenA

2007 Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses. Cell Host Microbe 2 404 416

26. ZhaoC

LouZ

GuoY

MaM

ChenY

2009 Nucleoside monophosphate complex structures of the endonuclease domain from the influenza virus polymerase PA subunit reveal the substrate binding site inside the catalytic center. J Virol 83 9024 9030

27. GarcinD

KolakofskyD

1990 A novel mechanism for the initiation of Tacaribe arenavirus genome replication. J Virol 64 6196 6203

28. NewmanM

StrzeleckaT

DornerLF

SchildkrautI

AggarwalAK

1994 Structure of restriction endonuclease BamHI and its relationship to EcoRI. Nature 368 660 664

29. PingoudA

FuxreiterM

PingoudV

WendeW

2005 Type II restriction endonucleases: structure and mechanism. Cell Mol Life Sci 62 685 707

30. LelkeM

BrunotteL

BuschC

GuntherS

2010 An N-terminal region of Lassa virus L protein plays a critical role in transcription but not replication of the virus genome. J Virol 84 1934 1944

31. GuilligayD

TarendeauF

Resa-InfanteP

ColomaR

CrepinT

2008 The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat Struct Mol Biol 15 500 506

32. AbrahamJ

CorbettKD

FarzanM

ChoeH

HarrisonSC

Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses. Nat Struct Mol Biol

33. De ClercqE

NeytsJ

2007 Avian influenza A (H5N1) infection: targets and strategies for chemotherapeutic intervention. Trends Pharmacol Sci 28 280 285

34. HsiehHP

HsuJT

2007 Strategies of development of antiviral agents directed against influenza virus replication. Curr Pharm Des 13 3531 3542

35. ParkesKE

ErmertP

FasslerJ

IvesJ

MartinJA

2003 Use of a pharmacophore model to discover a new class of influenza endonuclease inhibitors. J Med Chem 46 1153 1164

36. PowellHR

1999 The Rossmann Fourier autoindexing algorithm in MOSFLM. Acta Crystallogr D Biol Crystallogr 55 1690 1695

37. 1994 The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50 760 763

38. EmsleyP

CowtanK

2004 Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60 2126 2132

39. AltschulSF

MaddenTL

SchafferAA

ZhangJ

ZhangZ

1997 Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25 3389 3402

40. FinnRD

MistryJ

TateJ

CoggillP

HegerA

The Pfam protein families database. Nucleic Acids Res 38 D211 222

41. MaletH

CoutardB

JamalS

DutartreH

PapageorgiouN

2009 The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket. J Virol 83 6534 6545

42. HassM

GölnitzU

MüllerS

Becker-ZiajaB

GüntherS

2004 Replicon system for Lassa virus. J Virol 78 13793 13803

43. BuchholzUJ

FinkeS

ConzelmannKK

1999 Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter. J Virol 73 251 259

44. HassM

LelkeM

BuschC

Becker-ZiajaB

GüntherS

2008 Mutational evidence for a structural model of the Lassa virus RNA polymerase domain and identification of two residues, Gly1394 and Asp1395, that are critical for transcription but not replication of the genome. J Virol 82 10207 10217

45. SutterG

OhlmannM

ErfleV

1995 Non-replicating vaccinia vector efficiently expresses bacteriophage T7 RNA polymerase. FEBS Lett 371 9 12

46. Kabsch W Xds. Acta Crystallogr D Biol Crystallogr 66 125 132

47. EvansP

2006 Scaling and assessment of data quality. Acta Crystallogr D Biol Crystallogr 62 72 82

48. VonrheinC

BlancE

RoversiP

BricogneG

2007 Automated structure solution with autoSHARP. Methods Mol Biol 364 215 230

49. SchneiderTR

SheldrickGM

2002 Substructure solution with SHELXD. Acta Crystallogr D Biol Crystallogr 58 1772 1779

50. BricogneG

VonrheinC

FlensburgC

SchiltzM

PaciorekW

2003 Generation, representation and flow of phase information in structure determination: recent developments in and around SHARP 2.0. Acta Crystallogr D Biol Crystallogr 59 2023 2030

51. CowtanK

1994 An automated procedure for phase improvement by density modification. Joint CCP4 and ESF-EACBM Newsletter on Protein Crystallography 31 34 38

52. CowtanK

2006 The Buccaneer software for automated model building. 1. Tracing protein chains. Acta Crystallogr D Biol Crystallogr 62 1002 1011

53. AbrahamsJP

LeslieAG

1996 Methods used in the structure determination of bovine mitochondrial F1 ATPase. Acta Crystallogr D Biol Crystallogr 52 30 42

54. EmsleyP

LohkampB

ScottWG

CowtanK

Features and development of Coot. Acta Crystallogr D Biol Crystallogr 66 486 501

55. BricogneG

BlancE

BrandlM

FlensburgC

KellerP

2010 BUSTER version 2.X. Global Phasing Ltd Cambridge, United Kingdom

56. LeslieAG

1992 MOSFLM - Recent changes and future developments. Joint CCP4 and ESF-EACBM Newsletter on Protein Crystallography 35 18 19

57. MurshudovGN

VaginAA

DodsonEJ

1997 Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53 240 255

58. SmartO

BrandlM

FlensburgC

KellerP

PaciorekW

2008 Refinement with Local Structure Similarity Restraints (LSSR) Enables Exploitation of Information from Related Structures and Facilitates use of NCS. Annual Meeting of the American Crystallographic Association

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 9
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

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#