The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA

被引：423

作者：

Barbera, AJ

Chodaparambil, JV

Kelley-Clarke, B

Joukov, V

Walter, JC

Luger, K

Kaye, KM ^{[1
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA

[2] Colorado State Univ, Howard Hughes Med Inst, Ft Collins, CO 80523 USA

[3] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA

[4] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

来源：

SCIENCE | 2006年 / 311卷 / 5762期

关键词：

D O I：

10.1126/science.1120541

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

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.

引用

页码：856 / 861

页数：6

共 38 条

[1]

Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen [J].