NC - P7, Nucleocapsid protein

HIV NC binds to the HIV packaging signal on viral RNA and is sufficient for incorporation of RNA into virions.




PDB-1A1T: HIV-1 (isolate NL4-3) Nucleo-Capsid (Chain A) and SL3 Stem-loop RNA (Chain B) - produced using SwissModel/SPDBV/POVray

Key web links:
ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB: 1A1T (HIV-1 Nucleo-capsid)
UniProt: P04591 (HIV-1 HXB2 GAG)
Chime Tutorial: not available
HIV-1/Human Protein Interaction DB: HIV-1 Gag
Los Alamos HIV structure DB: Nucleocapsid protein
EMBL: K03455 [EMBL/GenBank/DDBJ]


Isoforms:

  • p7 (55 amino acids)


Cleavage sites:


Function:

  • Encapsulates and protects viral dimeric unspliced (genomic) RNA .
  • Nucleic acid condensing and chaperoning protein that binds to the virion genomic RNA (gRNA) and facilitates structural rearrangements of the genomic RNA in the course of replication by the viral reverse transcriptase .
  • Enhances various steps in reverse transcription including tRNA annealing and strand transfer .
  • Also plays a role in template switch, leading to recombination .
  • As part of the Gag polyprotein, NC participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly.
  • May also contribute to the initial binding of the bent form of Gag to the plasma
    membrane .

Localization:

  • Virion
  • Cell cytoplasm
  • Host nucleus (covers DNA flaps)

Additional Information:

  • Late timing of expression.
  • The HIV packaging signal consists of 4 stem-loop structures near the 5'-end of viral RNA.
  • The HIV packaging signal is sufficient to mediate the incorporation of heterologous RNA into virions .



Gag-NC Function & Host-Virus Protein Interactions:[TOP]




Interactions highlighted in the image:


Potential interactions (not in the image):


  • NC contains two zinc-finger motifs, which recognize the dimerization (DIS) and packaging (Psi) sequences, and interact with the 4 stem-loop structures of the HIV packaging signal . This allows for the dimerization and packaging of the genomic RNA .
  • NC binds to Actin during virus assembly.
  • Possibly interacts with reverse transcriptase .
  • DHX9 is involved in capsid assembly and HIV-1 RNA trafficking [see GUAVAh DHX9 interaction profile].


Genomic Location & Protein Sequence: [TOP]

HIV-1 (HXB2):

          10         20         30         40         50 
| | | | |
MQRGNFRNQR KIVKCFNCGK EGHTARNCRA PRKKGCWKCG KEGHQMKDCT ERQAN
[download in fasta format]

Length: 55 amino acids
Molecular Weight: 6425 Da
Theoretical pI: 10.08
Position relative to Gag protein: 378 - 432


Protein Domains/Folds/Motifs: [TOP]

InterPro signature for Retroviral NucleoCapsid protein Gag - IPR000721




Secondary Structure prediction:

Antigenic Sites - EMBOSS:



Predicted Motifs: Printer-friendly version

N-glycosylation:
N-myristoylation:
Amidation:
Protein kinase C:
Casein kinase II:
Tyrosine kinase:
cAMP / cGMP kinase:
Cell attachment motif:
Asp Protease motif:
Asp Prot Retro motif:
Cysteine-rich Region:
Tryptophan-rich Region:
Zinc-finger CCHC motif:
Leucine Zipper motif:

Primary and Secondary Database Entries: [TOP]

Identifiers:



ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB/MMDB: Search for HIV-1 & Nucleocapsid

UniProt: P04591 (HIV-1 HXB2 GAG)
EMBL: K03455; AAB50258.1 [EMBL/GenBank/DDBJ]

InterPro: IPR000721 - Retroviral Nuceocapsid p24 family
IPR001878 - Zinc-finger (CCHC-type) Domain
Pfam: PF00607 / PF00098
Prints: none
SCOP: SSF57756 Retroviral zinc finger-like domains
BLOCKS: P04591
Prosite: P04591
ProtoNet: P04591
Database of Interacting Proteins: P04591
ModBase: P04591
HIV-1/Human Protein Interaction DB: HIV-1 Gag
HIV-1 Sequence Database Los Alamos HIV Sequence Database

PDB:




Reviews and References: [TOP]

Cite the resource by citing the following paper:
Doherty R et al. BioAfrica's HIV-1 Proteomics Resource: Combining protein data with bioinformatics tools. Retrovirology (2005), 9;2(1):18.

1 - HIV Sequence Compendium 2000
Kuiken CL, Foley B, Hahn B, Korber B, Marx PA, McCutchan F, Mellors JW, Mullins JI, Sodroski J, Wolinksy S.
Theoretical Biol. & Biophys. Group, Los Alamos Nat Lab, LA-UR 01-3860 [Read it online: Compendium]
2 - Retroviruses
Coffin JM, Hughes SH, Varmus HE.
CD-ROM ed. (2002) Cold Spring Harbor Laboratory Press [Read it online: NCBI Bookshelf]
3 - Molecular Characteristics of HIV-1 Subtype C Viruses from KwaZulu-Natal, South Africa:
Implications for Vaccine and Antiretroviral Control Strategies.
Gordon M, De Oliveira T, Bishop K, Coovadia HM, Madurai L, Engelbrecht S, Janse van Rensburg E, Mosam A, Smith A, Cassol S.
Journal of Virology 77(4): 2587-2599 (2003) [pubmed: 12551997]
4 - The human immunodeficiency virus type 1 packaging signal and major splice donor region
have a conserved stable secondary structure.
Harrison GP, Lever AM.
J Virol 66: 4144-4153 (1992) [pubmed: 1602537]
5 - Gene transfer into human lymphocytes by a defective human immunodeficiency virus type 1 vector.
Poznansky M, Lever A, Bergeron L.
J Virol 65: 532-536 (1991) [pubmed: 1985215]
6 - Interactions between HIV-1 nucleocapsid protein and viral DNA may have important functions
in the viral life cycle.
Lapadat-Tapolsky M, De Rocquigny H, Van Gent D.
Nucleic Acids Res 21: 831-839 (1993) [pubmed: 8383840]
7 - The chaperoning and assistance roles of the HIV-1 nucleocapsid protein in proviral DNA synthesis and  maintenance.
Bampi C, Jacquenet S, Lener D, Décimo D, Darlix JL.
Int J Biochem Cell Biol. 36(9):1668-86 (2004). [pubmed: 15183337]
8 - Recombination during reverse transcription: an evaluation of the role of the nucleocapsid protein.
Negroni M, Buc H.
J Mol Biol. 286(1):15-31 (1999) [pubmed: 9931246]
9 - Retrospective on the all-in-one retroviral nucleocapsid protein.
Darlix JL, de Rocquigny H, Mauffret O, Mély Y.
Virus Res. 193:2-15 (2014) [pubmed: 24907482]
10 - Properties and functions of the nucleocapsid protein in virus assembly.
Muriaux D, Darlix JL.
RNA Biol. 7(6):744-53 (2010) [pubmed: 21157181]
11 - The tRNALys packaging complex in HIV-1.
Kleiman L, Cen S.
Int J Biochem Cell Biol. 36(9):1776-86 (2004) [pubmed: 15183344]
12 - Formation of immature and mature genomic RNA dimers in wild-type and protease-inactive HIV-1: differential roles of the Gag polyprotein, nucleocapsid proteins NCp15, NCp9, NCp7, and the dimerization initiation site.
Jalalirad M, Laughrea M.
Virology. 407(2):225-36 (2010) [pubmed: 20828778]
13 - The HIV-1 nucleocapsid protein recruits negatively charged lipids to ensure its optimal binding to lipid membranes.
Kempf N, Postupalenko V, Bora S, Didier P, Arntz Y, de Rocquigny H, Mély Y.
J Virol. 89(3):1756-67 (2015) [pubmed: 25410868]
14 - Nucleocapsid protein annealing of a primer-template enhances (+)-strand DNA synthesis and fidelity by HIV-1 reverse transcriptase.
Kim J, Roberts A, Yuan H, Xiong Y, Anderson KS.
J Mol Biol. 415(5):866-80 (2012) [pubmed: 22210155]
15 - The nucleocapsid region of HIV-1 Gag cooperates with the PTAP and LYPXnL late domains to recruit the cellular machinery necessary for viral budding.
Dussupt V, Javid MP, Abou-Jaoudé G, Jadwin JA, de La Cruz J, Nagashima K, Bouamr F.
PLoS Pathog. 5(3):e1000339 (2009) [pubmed: 19282983]
16 - The host protein Staufen1 interacts with the Pr55Gag zinc fingers and regulates HIV-1 assembly via its N-terminus.
Chatel-Chaix L, Boulay K, Mouland AJ, Desgroseillers L.
Retrovirology 5:41 (2008) [pubmed: 18498651]
17 - Basic residues in the nucleocapsid domain of Gag are required for interaction of HIV-1 gag with ABCE1 (HP68), a cellular protein important for HIV-1 capsid assembly.
Lingappa JR, Dooher JE, Newman MA, Kiser PK, Klein KC.
J Biol Chem. 281(7):3773-84 (2006) [pubmed: 16275648]
18 - Association of RNA helicase a with human immunodeficiency virus type 1 particles.
Roy BB, Hu J, Guo X, Russell RS, Guo F, Kleiman L, Liang C.
J Biol Chem. 281(18):12625-35 (2006) [pubmed: 16527808]
19 - ESCRT-II's involvement in HIV-1 genomic RNA trafficking and assembly.
Ghoujal B, Milev MP, Ajamian L, Abel K, Mouland AJ.
Biol Cell. 104(12):706-21 (2012) [pubmed: 22978549]
20 - Structure of the HIV-1 nucleocapsid protein bound to the SL3 psi-RNA recognition element.
De Guzman RN, Wu ZR, Stalling CC, Pappalardo L, Borer PN, Summers MF.
Science 279(5349):384-8 (1998) [pubmed: 9430589]



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Page last updated by Megan Druce, Paula Sommer and Tulio de Oliveira (UKZN/Africa Centre) & Philippe Le Mercier, Chantal Hulo and Patrick Masson (SIB/ViralZone).