10         20         30         40         50         60
         |          |          |          |          |          |
MGQTVTTPLS LTLGHWKDVE RIAHNQSVDV KKRRWVTFCS AEWPTFNVGW PRDGTFNRDL - 60
ITQVKIKVFS PGPHGHPDQV PYIVTWEALA FDPPPWVKPF VHPKPPPPLP PSAPSLPLEP - 120
PRSTPPRSSL YPALTPSLGA KPKPQVLSDS GGPLIDLLTE DPPPYRDPRP PPSDRDGNGG - 180
EATPAGEAPD PSPMASRLRG RREPPVADST TSQAFPLRAG GNGQLQYWPF SSSDLYNWKN - 240
NNPSFSEDPG KLTALIESVL ITHQPTWDDC QQLLGTLLTG EEKQRVLLEA RKAVRGDDGR - 300
PTQLPNEVDA AFPLERPDWD YTTQAGRNHL VHYRQLLLAG LQNAGRSPTN LAKVKGITQG - 360
PNESPSAFLE RLKEAYRRYT PYDPEDPGQE TNVSMSFIWQ SAPDIGRKLE RLEDLKNKTL - 420
GDLVREAEKI FNKRETPEER EERIRRETEE KEERRRTEDE QKEKERDRRR HREMSKLLAT - 480
VVSGQKQDRQ GGERRRSQLD RDQCAYCKEK GHWAKDCPKK PRGPRGPRPQ TSLLTLDDXG - 540
GQGQEPPPEP RITLKVGGQP VTFLVDTGAQ HSVLTQNPGP LSDKSAWVQG ATGGKRYRWT - 600
TDRKVHLATG KVTHSFLHVP DCPYPLLGRD LLTKLKAQIH FEGSGAQVMG PMGQPLQVLT - 660
LNIEDEHRLH ETSKEPDVSL GSTWLSDFPQ AWAETGGMGL AVRQAPLIIP LKATSTPVSI - 720
KQYPMSQEAR LGIKPHIQRL LDQGILVPCQ SPWNTPLLPV KKPGTNDYRP VQDLREVNKR - 780
VEDIHPTVPN PYNLLSGLPP SHQWYTVLDL KDAFFCLRLH PTSQPLFAFE WRDPEMGISG - 840
QLTWTRLPQG FKNSPTLFDE ALHRDLADFR IQHPDLILLQ YVDDLLLAAT SELDCQQGTR - 900
ALLQTLGNLG YRASAKKAQI CQKQVKYLGY LLKEGQRWLT EARKETVMGQ PTPKTPRQLR - 960
EFLGTAGFCR LWIPGFAEMA APLYPLTKTG TLFNWGPDQQ KAYQEIKQAL LTAPALGLPD - 1020
LTKPFELFVD EKQGYAKGVL TQKLGPWRRP VAYLSKKLDP VAAGWPPCLR MVAAIAVLTK - 1080
DAGKLTMGQP LVILAPHAVE ALVKQPPDRW LSNARMTHYQ ALLLDTDRVQ FGPVVALNPA - 1140
TLLPLPEEGL QHNCLDILAE AHGTRPDLTD QPLPDADHTW YTDGSSLLQE GQRKAGAAVT - 1200
TETEVIWAKA LPAGTSAQRA ELIALTQALK MAEGKKLNVY TDSRYAFATA HIHGEIYRRR - 1260
GLLTSEGKEI KNKDEILALL KALFLPKRLS IIHCPGHQKG HSAEARGNRM ADQAARKAAI - 1320
TETPDTSTLL IENSSPYTSE HFHYTVTDIK DLTKLGAIYD KTKKYWVYQG KPVMPDQFTF - 1380
ELLDFLHQLT HLSFSKMKAL LERSHSPYYM LNRDRTLKNI TETCKACAQV NASKSAVKQG - 1440
TRVRGHRPGT HWEIDFTEIK PGLYGYKYLL VFIDTFSGWI EAFPTKKETA KVVTKKLLEE - 1500
IFPRFGMPQV LGTDNGPAFV SKVSQTVADL LGIDWKLHCA YRPQSSGQVE RMNRTIKETL - 1560
TKLTLATGSR DWVLLLPLAL YRARNTPGPH GLTPYEILYG APPPLVNFPD PDMTRVTNSP - 1620
SLQAHLQALY LVQHEVWRPL AAAYQEQLDR PVVPHPYRVG DTVWVRRHQT KNLEPRWKGP - 1680
YTVLLTTPTA LKVDGIAAWI HAAHVKAADP GGGPSSRLTW RVQRSQNPLK IRLTREAP

Matrix protein p15 targets Gag and gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex. Capsid protein p30 forms the spherical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. Nucleocapsid protein p10 is involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization. The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5' end of the viral RNA. RT uses the 3' end of the tRNA primer to perfom a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perfom the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5' end of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primers. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allow the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.

DP00651 is the "parent" record of Gag-Pol polyprotein. Disorder has been characterized on a cleavage product described in "child" record DP00651_C007: Integrase p46.