Four major sequence elements of simian virus 40 large T antigen coordinate its specific and nonspecific DNA binding

Simmons, Daniel T.; Loeber, Gerhard; Tegtmeyer, Peter

doi:10.1128/jvi.64.5.1973-1983.1990

Cited by 77 publications

(44 citation statements)

References 49 publications

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“…Some viral proteins undergo nucleic acid-dependent oligomerization in a sequence-specific manner, an example of which is the Borna disease virus (BDV) nucleoprotein which requires the presence of 5′-specific BDV RNA for its oligomerization (Hock et al, 2010). Most famously, the main regulatory protein of all polyomaviruses, LT-Ag, binds to the origin of the viral DNA replication sequences in a double hexameric forms to initiate viral DNA replication (Auborn, Markowitz, Wang, Yu, & Prives, 1988;Lynch & Frisque, 1990;Simmons, Loeber, & Tegtmeyer, 1990;Simmons, et al 2004). , 2006).…”

Section: Stable Dimer and Oligomer Formation By Polyomavirus Agnoprmentioning

confidence: 99%

Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40

Sarıbaş

Coric

Bouaziz

et al. 2018

Journal Cellular Physiology

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Polyomavirus family consists of a highly diverse group of small DNA viruses. The founding family member (MPyV) was first discovered in the newborn mouse in the late 1950s, which induces solid tumors in a wide variety of tissue types that are the epithelial and mesenchymal origin. Later, other family members were also isolated from a number of mammalian, avian and fish species. Some of these viruses significantly contributed to our current understanding of the fundamentals of modern biology such as transcription, replication, splicing, RNA editing, and cell transformation. After the discovery of first two human polyomaviruses (JC virus [JCV] and BK virus [BKV]) in the early 1970s, there has been a rapid expansion in the number of human polyomaviruses in recent years due to the availability of the new technologies and brought the present number to 14. Some of the human polyomaviruses cause considerably serious human diseases, including progressive multifocal leukoencephalopathy, polyomavirus‐associated nephropathy, Merkel cell carcinoma, and trichodysplasia spinulosa. Emerging evidence suggests that the expression of the polyomavirus genome is more complex than previously thought. In addition to encoding universally expressed regulatory and structural proteins (LT‐Ag, Sm t‐Ag, VP1, VP2, and VP3), some polyomaviruses express additional virus‐specific regulatory proteins and microRNAs. This review summarizes the recent advances in polyomavirus genome expression with respect to the new viral proteins and microRNAs other than the universally expressed ones. In addition, a special emphasis is devoted to the recent structural and functional discoveries in the field of polyomavirus agnoprotein which is expressed only by JCV, BKV, and simian virus 40 genomes.

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Section: Stable Dimer and Oligomer Formation By Polyomavirus Agnoprmentioning

confidence: 99%

Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40

Sarıbaş

Coric

Bouaziz

et al. 2018

Journal Cellular Physiology

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“…We have mapped nonspecific DNA binding to a region between aa residues 131 and 517 (75). Recently, we showed that at least 5 residues (mapping between positions 149 and 203) within the DNA binding domain were important in binding nonspecifically to doubleand single-stranded DNAs (51,52). All mutations in the domain which significantly reduced nonspecific binding also prevented originspecific binding (although the converse was not true).…”

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confidence: 98%

Nonspecific DNA binding activity of simian virus 40 large T antigen: evidence for the cooperation of two regions for full activity

Lin

Upson

Simmons

1992

J Virol

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We generated a series of COOH-terminal truncated simian virus 40 large tumor (T) antigens by using oligonucleotide-directed site-specific mutagenesis. The mutant proteins [T(1-650) to T(1-516)] were expressed in insect cells infected with recombinant baculoviruses. T(1-623) and shorter proteins [T(1-621) to T(1-516)1 appeared to be structurally changed in a region between residues 269 and 522, as determined by increased sensitivities to trypsin digestion and by altered reactivities to several monoclonal antibodies. These same mutant proteins bound significantly less nonorigin plasmid DNA (15%) and calf thymus DNA (25%) than longer proteins [T(1-625) to T(1-708)]. However, all mutant T antigens exhibited a nearly wild-type level of viral origin-specific DNA binding and binding to a helicase substrate DNA. This indicated that binding to origin and helicase substrate DNAs is separable from about 85% of nonspecific binding to double-stranded DNA. As an independent confirmation that a region distinct from the origin-binding domain (amino acids 147 to 247) is * Corresponding author. origin-binding domain (residues 147 to about 247) (2, 49-52, 61) has been the best characterized. The maximal p53binding and helicase substrate-binding regions map to residues 272 to 517 (46) and 131 to 517 (75), respectively, and the ATP-binding region maps to amino acids (aa) 418 to 528 (4, 5). The first N-terminal 121 amino acids have been implicated in transactivation (57, 79), and a small region (residues 105 to 114) is responsible for binding to the Rb protein (13).One activity of T antigen that is less well characterized is its ability to bind nonspecifically to double-stranded and single-stranded DNAs (7,38,56). The exact function of this activity is not yet clear, but it has been implicated in origin-specific DNA binding (51). It may also be involved in subsequent steps during viral DNA replication, in the induction of cellular DNA synthesis, or in the activation of rRNA genes. We have mapped nonspecific DNA binding to a region between aa residues 131 and 517 (75). Recently, we showed that at least 5 residues (mapping between positions 149 and 203) within the DNA binding domain were important in binding nonspecifically to doubleand single-stranded DNAs (51,52). All mutations in the domain which significantly reduced nonspecific binding also prevented originspecific binding (although the converse was not true). This suggested that T antigen first binds to virus DNA nonspecifically and then locates the origin sequences.Several years ago, Prives et al. (44) reported that a 56-kDa adeno-SV40 hybrid protein (containing T-antigen sequences from about residues 252 to 708) bound calf thymus DNA but could not bind specifically to the SV40 origin. A smaller, 45-kDa protein, with T-antigen sequences from about residues 336 to 708 was unable to bind to any DNA. These 5443 Vol. 66,No. 9

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“…These activities include pro-tein oligomerization (74), binding to single-stranded DNA (49,75), interactions with cellular factors (31), and DNA unwinding and helicase activities (74,75,92). In light of this complexity, it is not surprising that the T-ag-bd is itself organized into subdomains (73). The solution structure of the T-ag-bd region between amino acids 131 and 260 (T-ag-bd 131-260 ) has provided preliminary insights into these processes (44).…”

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confidence: 99%

Purification of the simian virus 40 (SV40) T antigen DNA-binding domain and characterization of its interactions with the SV40 origin

Joo

Luo

Denis

et al. 1997

J Virol

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To better define protein-DNA interactions at a eukaryotic origin, the domain of simian virus 40 (SV40) large T antigen that specifically interacts with the SV40 origin has been purified and its binding to DNA has been characterized. Evidence is presented that the affinity of the purified T antigen DNA-binding domain for the SV40 origin is comparable to that of the full-length T antigen. Furthermore, stable binding of the T antigen DNA-binding domain to the SV40 origin requires pairs of pentanucleotide recognition sites separated by approximately one turn of a DNA double helix and positioned in a head-to-head orientation. Although two pairs of pentanucleotides are present in the SV40 origin, footprinting and band shift experiments indicate that binding is limited to dimer formation on a single pair of pentanucleotides. Finally, it is demonstrated that the T antigen DNA-binding domain interacts poorly with single-stranded DNA.

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Four major sequence elements of simian virus 40 large T antigen coordinate its specific and nonspecific DNA binding

Cited by 77 publications

References 49 publications

Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40

Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40

Nonspecific DNA binding activity of simian virus 40 large T antigen: evidence for the cooperation of two regions for full activity

Purification of the simian virus 40 (SV40) T antigen DNA-binding domain and characterization of its interactions with the SV40 origin

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