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Function of HIV Reverse transcriptase (RT)

RT is another important enzyme encoded by the pol gene [1].
To produce dsDNA from the viral single-stranded RNA genome, RT in the reverse transcriptase complex (RTC) catalyzes both the RNA-dependent and the DNA-dependent DNA polymerization reactions.
During reverse transcription, RT jumps from one template to another when two copies of single-stranded genomic RNAs exist per virion. The frequent template switch promotes the generation of novel recombinant DNA genome sequences derived from two parental RNA sequences [1].

Reference

Xue B, Mizianty MJ, Kurgan L, Uversky VN: Protein intrinsic disorder as a flexible armor and a weapon of HIV-1. Cell Mol Life Sci 2012, 69:1211-1259.(Download Article)

Sequence

(1) Reference sequence for HIV-1 Reverse transcriptase

Strain: HIV-1 subtype B HXB2 (ID: K03455)
Fasta format: Download
Reference sequence:

  1       10         20         30         40         50
  |        |          |          |          |          | 
  PISPIETVPV KLKPGMDGPK VKQWPLTEEK IKALVEICTE MEKEGKISKI 
  51      60         70         80         90         100
  |        |          |          |          |          | 
  GPENPYNTPV FAIKKKDSTK WRKLVDFREL NKRTQDFWEV QLGIPHPAGL 
  101    110        120        130        140        150
  |        |          |          |          |          | 
  KKKKSVTVLD VGDAYFSVPL DEDFRKYTAF TIPSINNETP GIRYQYNVLP 
  151    160        170        180        190        200
  |        |          |          |          |          | 
  QGWKGSPAIF QSSMTKILEP FRKQNPDIVI YQYMDDLYVG SDLEIGQHRT 
  201    210        220        230        240        250
  |        |          |          |          |          | 
  KIEELRQHLL RWGLTTPDKK HQKEPPFLWM GYELHPDKWT VQPIVLPEKD 
  251    260        270        280        290        300
  |        |          |          |          |          | 
  SWTVNDIQKL VGKLNWASQI YPGIKVRQLC KLLRGTKALT EVIPLTEEAE 
  301    310        320        330        340        350
  |        |          |          |          |          | 
  LELAENREIL KEPVHGVYYD PSKDLIAEIQ KQGQGQWTYQ IYQEPFKNLK 
  351    360        370        380        390        400
  |        |          |          |          |          | 
  TGKYARMRGA HTNDVKQLTE AVQKITTESI VIWGKTPKFK LPIQKETWET 
  401    410        420        430        440        450
  |        |          |          |          |          | 
  WWTEYWQATW IPEWEFVNTP PLVKLWYQLE KEPIVGAETF YVDGAANRET 
  451    460        470        480        490        500
  |        |          |          |          |          | 
  KLGKAGYVTN RGRQKVVTLT DTTNQKTELQ AIYLALQDSG LEVNIVTDSQ 
  501    510        520        530        540        550
  |        |          |          |          |          | 
  YALGIIQAQP DQSESELVNQ IIEQLIKKEK VYLAWVPAHK GIGGNEQVDK 
  551    560
  |        | 
  LVSAGIRKVL

(2) Reference sequence for HIV-2 and SIV Reverse transcriptase

Strain: SIV Mac239 (ID: M33262)
Fasta format: Download
Reference sequence:

  1       10         20         30         40         50
  |        |          |          |          |          | 
  PIAKVEPVKV ALKPGKDGPK LKQWPLSKEK IVALREICEK MEKDGQLEEA 
  51      60         70         80         90         100
  |        |          |          |          |          | 
  PPTNPYNTPT FAIKKKDKNK WRMLIDFREL NRVTQDFTEV QLGIPHPAGL 
  101    110        120        130        140        150
  |        |          |          |          |          | 
  AKRKRITVLD IGDAYFSIPL DEEFRQYTAF TLPSVNNAEP GKRYIYKVLP 
  151    160        170        180        190        200
  |        |          |          |          |          | 
  QGWKGSPAIF QYTMRHVLEP FRKANPDVTL VQYMDDILIA SDRTDLEHDR 
  201    210        220        230        240        250
  |        |          |          |          |          | 
  VVLQSKELLN SIGFSTPEEK FQKDPPFQWM GYELWPTKWK LQKIELPQRE 
  251    260        270        280        290        300
  |        |          |          |          |          | 
  TWTVNDIQKL VGVLNWAAQI YPGIKTKHLC RLIRGKMTLT EEVQWTEMAE 
  301    310        320        330        340        350
  |        |          |          |          |          | 
  AEYEENKIIL SQEQEGCYYQ EGKPLEATVI KSQDNQWSYK IHQEDKILKV 
  351    360        370        380        390        400
  |        |          |          |          |          | 
  GKFAKIKNTH TNGVRLLAHV IQKIGKEAIV IWGQVPKFHL PVEKDVWEQW 
  401    410        420        430        440        450
  |        |          |          |          |          | 
  WTDYWQVTWI PEWDFISTPP LVRLVFNLVK DPIEGEETYY TDGSCNKQSK 
  451    460        470        480        490        500
  |        |          |          |          |          | 
  EGKAGYITDR GKDKVKVLEQ TTNQQAELEA FLMALTDSGP KANIIVDSQY 
  501    510        520        530        540        550
  |        |          |          |          |          | 
  VMGIITGCPT ESESRLVNQI IEEMIKKSEI YVAWVPAHKG IGGNQEIDHL 
  551   559
  |       |
  VSQGIRQVL

(3) Coloring scheme for above amino acids

Amino acids with hydrophobic side chains (normally buried inside the protein core):
- A - Ala - Alanine
- I - Ile - Isoleucine
- L - Leu - Leucine
- M - Met - Methionine
- V - Val - Valine
Amino acids with polar uncharged side chains (may participate in hydrogen bonds):
- N - Asn - Asparagine
- Q - Gln - Glutamine
- S - Ser - Serine
- T - Thr - Threonine
Amino acids with positive charged side chains:
- H - His - Histidine
- K - Lys - Lysine
- R - Arg - Arginine
Amino acids with negative charged side chains:
- D - Asp - Aspartic acid
- E - Glu - Glutamic acid
Amino acids with aromatic side chains:
- F - Phe - Phenylalanine
- Y - Tyr - Tyrosine
- W - Trp - Tryptophan
Cysteine: C - Cys - Cysteine
Glycine: G - Gly - Glycine
Proline: P - Pro - Proline

Amino acid variations at HIV-1 Reverse transcriptase

Here, we visualize the prevalence of amino acid variations at the HIV-1 Reverse transcriptase from HIV-1 subtype B.

Protocal of our sequence collection

For HIV-1 subtype B, one sequence per patient was extracted from HIV Los Alamos database (www.hiv.lanl.gov/).
We removed misclassified sequences or sequences with hypermutations, stop codons, ambiguous nucleotides, which were described in our article [1].
We removed sequences conferred partial or full resistance to any of the Reverse transcriptase inhibitors, RT inhibitors and integrase inhibitors using HIVdb V6.0 .

Visualization

Our sequence dataset of HIV-1 subtype B Reverse transcriptase included 4725 sequences. In the following picture, HXB2 indices of individual proteins are shown on top of the colored bars. A consensus amino acid at each position is shown beneath the colored bar. Natural variations are shown below the consensus amino acids; proportions (%) are colored red if they were more than 5%; blue otherwise.

HIV-1 protein interaction patterns.

www.virusface.com

Please cite our article:

Guangdi Li, Supinya Piampongsant, Nuno Rodrigues Faria, Arnout Voet, Andrea-Clemencia Pineda-Peña, Ricardo Khouri, Philippe Lemey, Anne-Mieke Vandamme, Kristof Theys. An integrated map of HIV genome-wide variation from a population perspective. Retrovirology 12, 18, doi:10.1186/s12977-015-0148-6 (2015). [PDF] [PubMed Link]

Structure

(1) Secondary structure of HIV-1 Reverse transcriptase

Here, we visualize the secondary structure of HIV-1 Reverse transcriptase using PDBSum (PDB code: 1N6Q)

(2) Tertiary structure of HIV-1 Reverse transcriptase

Here, we provide a structure movie of Reverse transcriptase using PyMOL V1.7 (PDB code: 1N6Q). Alpha-helix and beta-strand secondary structures are demonstrated by red .

Localization

(1) Coding region of Reverse transcriptase at the HIV genome

(2) Localization of Reverse transcriptase during the HIV-1 life cycle

Here, we visualize the localization of Reverse transcriptase during the viral life cycle. Red stars indicate the appearance of HIV-1 Reverse transcriptase.

Function of HIV Reverse transcriptase (RT)

RT is another important enzyme encoded by the pol gene [1].

To produce dsDNA from the viral single-stranded RNA genome, RT in the reverse transcriptase complex (RTC) catalyzes both the RNA-dependent and the DNA-dependent DNA polymerization reactions.

During reverse transcription, RT jumps from one template to another when two copies of single-stranded genomic RNAs exist per virion. The frequent template switch promotes the generation of novel recombinant DNA genome sequences derived from two parental RNA sequences [1].

Reference

Xue B, Mizianty MJ, Kurgan L, Uversky VN: Protein intrinsic disorder as a flexible armor and a weapon of HIV-1. Cell Mol Life Sci 2012, 69:1211-1259.(Download Article)

Sequence

(1) Reference sequence for HIV-1 Reverse transcriptase

Strain: HIV-1 subtype B HXB2 (ID: K03455)

Fasta format: Download

Reference sequence:

(2) Reference sequence for HIV-2 and SIV Reverse transcriptase

Strain: SIV Mac239 (ID: M33262)

Fasta format: Download

Reference sequence:

(3) Coloring scheme for above amino acids

Amino acids with hydrophobic side chains (normally buried inside the protein core):

A - Ala - Alanine

I - Ile - Isoleucine

L - Leu - Leucine

M - Met - Methionine

V - Val - Valine

Amino acids with polar uncharged side chains (may participate in hydrogen bonds):

N - Asn - Asparagine

Q - Gln - Glutamine

S - Ser - Serine

T - Thr - Threonine

Amino acids with positive charged side chains:

H - His - Histidine

K - Lys - Lysine

R - Arg - Arginine

Amino acids with negative charged side chains:

D - Asp - Aspartic acid

E - Glu - Glutamic acid

Amino acids with aromatic side chains:

F - Phe - Phenylalanine

Y - Tyr - Tyrosine

W - Trp - Tryptophan

Cysteine: C - Cys - Cysteine

Glycine: G - Gly - Glycine

Proline: P - Pro - Proline

Amino acid variations at HIV-1 Reverse transcriptase

Here, we visualize the prevalence of amino acid variations at the HIV-1 Reverse transcriptase from HIV-1 subtype B.

Protocal of our sequence collection

For HIV-1 subtype B, one sequence per patient was extracted from HIV Los Alamos database (www.hiv.lanl.gov/).

We removed misclassified sequences or sequences with hypermutations, stop codons, ambiguous nucleotides, which were described in our article [1].

We removed sequences conferred partial or full resistance to any of the Reverse transcriptase inhibitors, RT inhibitors and integrase inhibitors using HIVdb V6.0 .

Visualization

HIV-1 protein interaction patterns.

www.virusface.com

Please cite our article:

Structure

(1) Secondary structure of HIV-1 Reverse transcriptase

Here, we visualize the secondary structure of HIV-1 Reverse transcriptase using PDBSum (PDB code: 1N6Q)

(2) Tertiary structure of HIV-1 Reverse transcriptase

Here, we provide a structure movie of Reverse transcriptase using PyMOL V1.7 (PDB code: 1N6Q). Alpha-helix and beta-strand secondary structures are demonstrated by red . I'm sorry; your browser doesn't support HTML5 video in WebM with VP8 or MP4 with H.264.

Localization

(1) Coding region of Reverse transcriptase at the HIV genome

(2) Localization of Reverse transcriptase during the HIV-1 life cycle

Here, we visualize the localization of Reverse transcriptase during the viral life cycle. Red stars indicate the appearance of HIV-1 Reverse transcriptase.

Anti-HIV inhibitor

(1) Drug binding pocket of HIV-1 Reverse transcriptase

Here, we visualize the drug binding pocket of HIV-1 Reverse transcriptase

(2) List of known inhibitors targeting HIV-1 Reverse transcriptase

Here, we summarize the published anti-HIV inhibitors which bind to HIV-1 Reverse transcriptase.

Protein-protein interactions

Here, we provide a structure movie of Reverse transcriptase using PyMOL V1.7 (PDB code: 1N6Q). Alpha-helix and beta-strand secondary structures are demonstrated by red .