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Science 10 February 2006:
Vol. 311. no. 5762, pp. 856 - 861
DOI: 10.1126/science.1120541
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Reports

The Nucleosomal Surface as a Docking Station for Kaposi's Sarcoma Herpesvirus LANA

Andrew J. Barbera,1* Jayanth V. Chodaparambil,2* Brenna Kelley-Clarke,1 Vladimir Joukov,3 Johannes C. Walter,4 Karolin Luger,2 Kenneth M. Kaye1{dagger}

Kaposi's sarcoma–associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) mediates viral genome attachment to mitotic chromosomes. We find that N-terminal LANA docks onto chromosomes by binding nucleosomes through the folded region of histones H2A-H2B. The same LANA residues were required for both H2A-H2B binding and chromosome association. Further, LANA did not bind Xenopus sperm chromatin, which is deficient in H2A-H2B; chromatin binding was rescued after assembly of nucleosomes containing H2A-H2B. We also describe the 2.9-angstrom crystal structure of a nucleosome complexed with the first 23 LANA amino acids. The LANA peptide forms a hairpin that interacts exclusively with an acidic H2A-H2B region that is implicated in the formation of higher order chromatin structure. Our findings present a paradigm for how nucleosomes may serve as binding platforms for viral and cellular proteins and reveal a previously unknown mechanism for KSHV latency.

1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
2 Howard Hughes Medical Institute and Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523–1870, USA.
3 Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
4 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: kkaye{at}rics.bwh.harvard.edu

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