The 3D structure of Kaposi sarcoma herpesvirus LANA C-terminal domain bound to DNA.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Schulz, Thomas F
MetadataShow full item record
AbstractKaposi sarcoma herpesvirus (KSHV) persists as a latent nuclear episome in dividing host cells. This episome is tethered to host chromatin to ensure proper segregation during mitosis. For duplication of the latent genome, the cellular replication machinery is recruited. Both of these functions rely on the constitutively expressed latency-associated nuclear antigen (LANA) of the virus. Here, we report the crystal structure of the KSHV LANA DNA-binding domain (DBD) in complex with its high-affinity viral target DNA, LANA binding site 1 (LBS1), at 2.9 Å resolution. In contrast to homologous proteins such as Epstein-Barr virus nuclear antigen 1 (EBNA-1) of the related γ-herpesvirus Epstein-Barr virus, specific DNA recognition by LANA is highly asymmetric. In addition to solving the crystal structure, we found that apart from the two known LANA binding sites, LBS1 and LBS2, LANA also binds to a novel site, denoted LBS3. All three sites are located in a region of the KSHV terminal repeat subunit previously recognized as a minimal replicator. Moreover, we show that the LANA DBD can coat DNA of arbitrary sequence by virtue of a characteristic lysine patch, which is absent in EBNA-1 of the Epstein-Barr virus. Likely, these higher-order assemblies involve the self-association of LANA into supermolecular spirals. One such spiral assembly was solved as a crystal structure of 3.7 Å resolution in the absence of DNA. On the basis of our data, we propose a model for the controlled nucleation of higher-order LANA oligomers that might contribute to the characteristic subnuclear KSHV microdomains ("LANA speckles"), a hallmark of KSHV latency.
CitationThe 3D structure of Kaposi sarcoma herpesvirus LANA C-terminal domain bound to DNA. 2015, 112 (21):6694-9 Proc. Natl. Acad. Sci. U.S.A.
The following license files are associated with this item:
- Site-specific association with host and viral chromatin by Kaposi's sarcoma-associated herpesvirus LANA and its reversal during lytic reactivation.
- Authors: Mercier A, Arias C, Madrid AS, Holdorf MM, Ganem D
- Issue date: 2014 Jun
- Mutational analysis of the latency-associated nuclear antigen DNA-binding domain of Kaposi's sarcoma-associated herpesvirus reveals structural conservation among gammaherpesvirus origin-binding proteins.
- Authors: Han SJ, Hu J, Pierce B, Weng Z, Renne R
- Issue date: 2010 Sep
- Kaposi's sarcoma-associated herpesvirus-encoded LANA recruits topoisomerase IIβ for latent DNA replication of the terminal repeats.
- Authors: Purushothaman P, McDowell ME, McGuinness J, Salas R, Rumjahn SM, Verma SC
- Issue date: 2012 Sep
- A structural basis for BRD2/4-mediated host chromatin interaction and oligomer assembly of Kaposi sarcoma-associated herpesvirus and murine gammaherpesvirus LANA proteins.
- Authors: Hellert J, Weidner-Glunde M, Krausze J, Richter U, Adler H, Fedorov R, Pietrek M, Rückert J, Ritter C, Schulz TF, Lührs T
- Issue date: 2013
- The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus supports latent DNA replication in dividing cells.
- Authors: Hu J, Garber AC, Renne R
- Issue date: 2002 Nov