Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen
The DNA tumor virus Simian virus 40 (SV40) is a model system for studying eukaryotic replication. SV40 large tumor antigen (LTag) is the initiator/helicase that is essential for genome replication. LTag recognizes and assembles at the viral replication origin. We determined the structure of two mult...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713001095 |
| _version_ | 1818231011991879680 |
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| author | Y. Paul Chang Meng Xu Ana Carolina Dantas Machado Xian Jessica Yu Remo Rohs Xiaojiang S. Chen |
| author_facet | Y. Paul Chang Meng Xu Ana Carolina Dantas Machado Xian Jessica Yu Remo Rohs Xiaojiang S. Chen |
| author_sort | Y. Paul Chang |
| collection | DOAJ |
| description | The DNA tumor virus Simian virus 40 (SV40) is a model system for studying eukaryotic replication. SV40 large tumor antigen (LTag) is the initiator/helicase that is essential for genome replication. LTag recognizes and assembles at the viral replication origin. We determined the structure of two multidomain LTag subunits bound to origin DNA. The structure reveals that the origin binding domains (OBDs) and Zn and AAA+ domains are involved in origin recognition and assembly. Notably, the OBDs recognize the origin in an unexpected manner. The histidine residues of the AAA+ domains insert into a narrow minor groove region with enhanced negative electrostatic potential. Computational analysis indicates that this region is intrinsically narrow, demonstrating the role of DNA shape readout in origin recognition. Our results provide important insights into the assembly of the LTag initiator/helicase at the replication origin and suggest that histidine contacts with the minor groove serve as a mechanism of DNA shape readout. |
| first_indexed | 2024-12-12T10:43:37Z |
| format | Article |
| id | doaj.art-fb04f728d0c64f5ca115b0b3c00ad683 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T10:43:37Z |
| publishDate | 2013-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-fb04f728d0c64f5ca115b0b3c00ad6832022-12-22T00:26:59ZengElsevierCell Reports2211-12472013-04-01341117112710.1016/j.celrep.2013.03.002Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor AntigenY. Paul Chang0Meng Xu1Ana Carolina Dantas Machado2Xian Jessica Yu3Remo Rohs4Xiaojiang S. Chen5Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USAGraduate Program in Genetics, Molecular and Cell Biology, University of Southern California, Los Angeles, CA 90089, USAMolecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USAMolecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USAMolecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USAMolecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USAThe DNA tumor virus Simian virus 40 (SV40) is a model system for studying eukaryotic replication. SV40 large tumor antigen (LTag) is the initiator/helicase that is essential for genome replication. LTag recognizes and assembles at the viral replication origin. We determined the structure of two multidomain LTag subunits bound to origin DNA. The structure reveals that the origin binding domains (OBDs) and Zn and AAA+ domains are involved in origin recognition and assembly. Notably, the OBDs recognize the origin in an unexpected manner. The histidine residues of the AAA+ domains insert into a narrow minor groove region with enhanced negative electrostatic potential. Computational analysis indicates that this region is intrinsically narrow, demonstrating the role of DNA shape readout in origin recognition. Our results provide important insights into the assembly of the LTag initiator/helicase at the replication origin and suggest that histidine contacts with the minor groove serve as a mechanism of DNA shape readout.http://www.sciencedirect.com/science/article/pii/S2211124713001095 |
| spellingShingle | Y. Paul Chang Meng Xu Ana Carolina Dantas Machado Xian Jessica Yu Remo Rohs Xiaojiang S. Chen Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen Cell Reports |
| title | Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen |
| title_full | Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen |
| title_fullStr | Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen |
| title_full_unstemmed | Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen |
| title_short | Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen |
| title_sort | mechanism of origin dna recognition and assembly of an initiator helicase complex by sv40 large tumor antigen |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713001095 |
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