The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA.
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.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Andrew J
AJ
Barbera
Jayanth V
JV
Chodaparambil
Brenna
B
Kelley-Clarke
Vladimir
V
Joukov
Johannes C
JC
Walter
Karolin
K
Luger
Kenneth M
KM
Kaye
D019943:Amino Acid Substitution; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism; D002877:Chromosomes, Human / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D019288:Herpesvirus 8, Human / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014982:Xenopus laevis
D000956:Antigens, Viral; D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D011993:Recombinant Fusion Proteins; C109540:latency-associated nuclear antigen