DP00615_C010: Non-structural protein 5A [cleavage product 10]FASTA viewXML view

General information
DisProt:DP00615_C010
Name:Non-structural protein 5A [cleavage product 10]
Synonym(s):POLG_HCVCO
NS5A
p56
cleavage product 10 of Genome polyprotein
First appeared in release:Release 5.4 (10/14/2010)
UniProt:Q9WMX2
UniGene: 
SwissProt: POLG_HCVCO
TrEMBL:  
NCBI (GI):  
Source organism:Hepatitis C virus genotype 1b (isolate Con1) (HCV)
Sequence length:447
Percent disordered:89%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
SGSWLRDVWD WICTVLTDFK TWLQSKLLPR LPGVPFFSCQ RGYKGVWRGD GIMQTTCPCG - 60
AQITGHVKNG SMRIVGPRTC SNTWHGTFPI NAYTTGPCTP SPAPNYSRAL WRVAAEEYVE - 120
VTRVGDFHYV TGMTTDNVKC PCQVPAPEFF TEVDGVRLHR YAPACKPLLR EEVTFLVGLN - 180
QYLVGSQLPC EPEPDVAVLT SMLTDPSHIT AETAKRRLAR GSPPSLASSS ASQLSAPSLK - 240
ATCTTRHDSP DADLIEANLL WRQEMGGNIT RVESENKVVI LDSFEPLQAE EDEREVSVPA - 300
EILRRSRKFP RAMPIWARPD YNPPLLESWK DPDYVPPVVH GCPLPPAKAP PIPPPRRKRT - 360
VVLSESTVSS ALAELATKTF GSSESSAVDS GTATASPDQP SDDGDAGSDV ESYSSMPPLE - 420
GEPGDPDLSD GSWSTVSEEA SEDVVCC



Functional narrative    

NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication By similarity. (UniProt). NS5A is cleavage product 10 of Genome polyprotein, comprising aa 1973-2419 of the polyprotein.

Region 1: 1-213 Region 2: 250-342 Region 3: 356-447

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 1
Type:Disordered
Name:Domain I
Location:1 - 213
Length:213
Region sequence:

SGSWLRDVWDWICTVLTDFKTWLQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMQTTCPCG
AQITGHVKNGSMRIVGPRTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYVE
VTRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLLREEVTFLVGLN
QYLVGSQLPCEPEPDVAVLTSMLTDPSHITAET

Modification type: Engineered
Fragment
PDB: 1ZH1:A, 3FQM:A, 3FQQ:A
Structural/functional type: Function arises from the disordered state
Functional classes: Chaperones
Molecular assembly
Functional subclasses: Flexible linkers/spacers
Substrate/ligand binding
Protein-protein binding
Metal binding
Protein-RNA binding
Detection methods:
  1. X-ray crystallography (277 K; pH: 7; HEPES; isopropanol; non-detergent sulphobetaine 201; trisodium citrate)

  2. X-ray crystallography (277 K; pH: 7.5; HEPES 0.1 M; isopropanol (10% v/v); N-nonylphosphocholine ((FOS-CHOLINE-9 from Hampton screen 3, No. 18)); PEG-3350 22 %)
References:
  1. Love RA, Brodsky O, Hickey MJ, Wells PA, Cronin CN. "Crystal structure of a novel dimeric form of NS5A domain I protein from hepatitis C virus." J. Virol.. 2009; 83(9): 4395-403. PubMed: 19244328

  2. Tellinghuisen TL, Foss KL, Treadaway JC, Rice CM. "Identification of residues required for RNA replication in domains II and III of the hepatitis C virus NS5A protein." J. Virol.. 2007; 82(3): 1073-83. PubMed: 18032500

  3. Tellinghuisen TL, Marcotrigiano J, Gorbalenya AE, Rice CM. "The NS5A protein of hepatitis C virus is a zinc metalloprotein." J. Biol. Chem.. 2004; 279(47): 48576-87. PubMed: 15339921

  4. Tellinghuisen TL, Marcotrigiano J, Rice CM. "Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase." Nature. 2005; 435(7040): 374-9. PubMed: 15902263
Comments:
Tellinghuisen et al (2005), used a construct of domain 1 consisting of aa 25-215, whereas Love et al (2009) used a construct consisting of aa 33-202.

Domain I contains an amphipathic N-terminal helix at aa 1-27 that promotes membrane association and contains a zinc-binding motif.


Region 2
Type:Disordered
Name:Domain II
Location:250 - 342
Length:93
Region sequence:

PDADLIEANLLWRQEMGGNITRVESENKVVILDSFEPLQAEEDEREVSVPAEILRRSRKF
PRAMPIWARPDYNPPLLESWKDPDYVPPVVHGC

Modification type: Engineered
Fragment
PDB: 1ZH1:A
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular assembly
Chaperones
Functional subclasses: Apoptosis Regulation
Protein-protein binding
Detection methods:
  1. X-ray crystallography (277 K; pH: 7; HEPES; isopropanol; non-detergent sulphobetaine 201; trisodium citrate)
References:
  1. Tellinghuisen TL, Foss KL, Treadaway JC, Rice CM. "Identification of residues required for RNA replication in domains II and III of the hepatitis C virus NS5A protein." J. Virol.. 2007; 82(3): 1073-83. PubMed: 18032500

  2. Tellinghuisen TL, Marcotrigiano J, Gorbalenya AE, Rice CM. "The NS5A protein of hepatitis C virus is a zinc metalloprotein." J. Biol. Chem.. 2004; 279(47): 48576-87. PubMed: 15339921

  3. Tellinghuisen TL, Marcotrigiano J, Rice CM. "Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase." Nature. 2005; 435(7040): 374-9. PubMed: 15902263
Comments:
 



Region 3
Type:Disordered
Name:Domain III
Location:356 - 447
Length:92
Region sequence:

RRKRTVVLSESTVSSALAELATKTFGSSESSAVDSGTATASPDQPSDDGDAGSDVESYSS
MPPLEGEPGDPDLSDGSWSTVSEEASEDVVCC

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Modification site
Molecular assembly
Functional subclasses: Unknown
Phosphorylation
Detection methods:
 
References:
  1. Tellinghuisen TL, Foss KL, Treadaway JC, Rice CM. "Identification of residues required for RNA replication in domains II and III of the hepatitis C virus NS5A protein." J. Virol.. 2007; 82(3): 1073-83. PubMed: 18032500

  2. Tellinghuisen TL, Marcotrigiano J, Gorbalenya AE, Rice CM. "The NS5A protein of hepatitis C virus is a zinc metalloprotein." J. Biol. Chem.. 2004; 279(47): 48576-87. PubMed: 15339921

  3. Tellinghuisen TL, Marcotrigiano J, Rice CM. "Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase." Nature. 2005; 435(7040): 374-9. PubMed: 15902263
Comments:
 



Comments


NOTE on Organism: DP00588 is organism Hepatitis C virus genotype 1a (isolate H) (HCV), aka HCVH; DP00615 is Hepatitis C virus genotype 1b (isolate Con1) (HCV) aka HCV1b or HCVCO. These entries share 85% identity.


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