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Host Proteins Ku and HMGA1 As Participants of HIV-1 Transcription.

Shadrina OA, Knyazhanskaya ES, Korolev SP, Gottikh MB - Acta Naturae (2016 Jan-Mar)

Bottom Line: The latency maintenance is also a problematic question.We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1.Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, Moscow, 119991, Russia.

ABSTRACT
Human immunodeficiency virus type 1 is known to use the transcriptional machinery of the host cell for viral gene transcription, and the only viral protein that partakes in this process is Tat, the viral trans-activator of transcription. During acute infection, the binding of Tat to the hairpin at the beginning of the transcribed viral RNA recruits the PTEFb complex, which in turn hyperphosphorylates RNA-polymerase II and stimulates transcription elongation. Along with acute infection, HIV-1 can also lead to latent infection that is characterized by a low level of viral transcription. During the maintenance and reversal of latency, there are no detectable amounts of Tat protein in the cell and the mechanism of transcription activation in the absence of Tat protein remains unclear. The latency maintenance is also a problematic question. It seems evident that cellular proteins with a yet unknown nature or role regulate both transcriptional repression in the latent phase and its activation during transition into the lytic phase. The present review discusses the role of cellular proteins Ku and HMGA1 in the initiation of transcription elongation of the HIV-1 provirus. The review presents data regarding Ku-mediated HIV-1 transcription and its dependence on the promoter structure and the shape of viral DNA. We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1. Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

No MeSH data available.


Related in: MedlinePlus

Structure of the Ku heterodimer in a complex with DNA according to[26]. DNA(shown in black) resides in the channel formed by Ku70 (shown in yellow) andKu80 (shown in brown). PDBID 1JEY
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Figure 3: Structure of the Ku heterodimer in a complex with DNA according to[26]. DNA(shown in black) resides in the channel formed by Ku70 (shown in yellow) andKu80 (shown in brown). PDBID 1JEY

Mentions: The Ku70/Ku80 heterodimer is a DNA-binding protein that mostly interacts withthe free ends of doublestranded DNA, and its biological function is mainlyrelated to this feature. The interaction between the Ku heterodimer and DNA israther strong: the Kd value varies within a range of1.5–4.0 × 10-10 M [25].According to X-ray data [26], Ku70 andKu80 within a heterodimer form an asymmetricring with a wide base and a thin bridge; the resulting channel is big enough toencircle DNA (Fig. 3).The channel predominantly consists ofpositively charged amino acid residues that interact with the negativelycharged sugar-phosphate backbone of the DNA molecule, which explains why Ku canbind DNA in a sequence-independent manner. After binding to the DNA end, Ku canmigrate (slide) along DNA and pause at certain sequences[25, 27].


Host Proteins Ku and HMGA1 As Participants of HIV-1 Transcription.

Shadrina OA, Knyazhanskaya ES, Korolev SP, Gottikh MB - Acta Naturae (2016 Jan-Mar)

Structure of the Ku heterodimer in a complex with DNA according to[26]. DNA(shown in black) resides in the channel formed by Ku70 (shown in yellow) andKu80 (shown in brown). PDBID 1JEY
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837570&req=5

Figure 3: Structure of the Ku heterodimer in a complex with DNA according to[26]. DNA(shown in black) resides in the channel formed by Ku70 (shown in yellow) andKu80 (shown in brown). PDBID 1JEY
Mentions: The Ku70/Ku80 heterodimer is a DNA-binding protein that mostly interacts withthe free ends of doublestranded DNA, and its biological function is mainlyrelated to this feature. The interaction between the Ku heterodimer and DNA israther strong: the Kd value varies within a range of1.5–4.0 × 10-10 M [25].According to X-ray data [26], Ku70 andKu80 within a heterodimer form an asymmetricring with a wide base and a thin bridge; the resulting channel is big enough toencircle DNA (Fig. 3).The channel predominantly consists ofpositively charged amino acid residues that interact with the negativelycharged sugar-phosphate backbone of the DNA molecule, which explains why Ku canbind DNA in a sequence-independent manner. After binding to the DNA end, Ku canmigrate (slide) along DNA and pause at certain sequences[25, 27].

Bottom Line: The latency maintenance is also a problematic question.We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1.Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, Moscow, 119991, Russia.

ABSTRACT
Human immunodeficiency virus type 1 is known to use the transcriptional machinery of the host cell for viral gene transcription, and the only viral protein that partakes in this process is Tat, the viral trans-activator of transcription. During acute infection, the binding of Tat to the hairpin at the beginning of the transcribed viral RNA recruits the PTEFb complex, which in turn hyperphosphorylates RNA-polymerase II and stimulates transcription elongation. Along with acute infection, HIV-1 can also lead to latent infection that is characterized by a low level of viral transcription. During the maintenance and reversal of latency, there are no detectable amounts of Tat protein in the cell and the mechanism of transcription activation in the absence of Tat protein remains unclear. The latency maintenance is also a problematic question. It seems evident that cellular proteins with a yet unknown nature or role regulate both transcriptional repression in the latent phase and its activation during transition into the lytic phase. The present review discusses the role of cellular proteins Ku and HMGA1 in the initiation of transcription elongation of the HIV-1 provirus. The review presents data regarding Ku-mediated HIV-1 transcription and its dependence on the promoter structure and the shape of viral DNA. We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1. Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

No MeSH data available.


Related in: MedlinePlus