Atomic Structure of Human Adenovirus by Cryo-EM Reveals Interactions Among Protein Networks

被引:275
作者
Liu, Hongrong [1 ,2 ,3 ]
Jin, Lei [1 ,2 ]
Koh, Sok Boon S. [4 ]
Atanasov, Ivo [2 ]
Schein, Stan [2 ,5 ,6 ]
Wu, Lily [2 ,4 ]
Zhou, Z. Hong [1 ,2 ]
机构
[1] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA
[3] Xiangtan Univ, Inst Modern Phys, Xiangtan 411105, Hunan, Peoples R China
[4] Univ Calif Los Angeles, Sch Med, Inst Mol Med IMED, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA
[6] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA
基金
美国国家卫生研究院;
关键词
CRYOELECTRON MICROSCOPY STRUCTURE; RESOLUTION; HEXON; VECTORS; TYPE-2; DNA; IX; BACTERIOPHAGE-PRD1; VISUALIZATION; ORGANIZATION;
D O I
10.1126/science.1187433
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 ; 0710 ; 09 ;
摘要
Construction of a complex virus may involve a hierarchy of assembly elements. Here, we report the structure of the whole human adenovirus virion at 3.6 angstroms resolution by cryo-electron microscopy (cryo-EM), revealing in situ atomic models of three minor capsid proteins (IIIa, VIII, and IX), extensions of the (penton base and hexon) major capsid proteins, and interactions within three protein-protein networks. One network is mediated by protein IIIa at the vertices, within group-of-six (GOS) tiles-a penton base and its five surrounding hexons. Another is mediated by ropes (protein IX) that lash hexons together to form group-of-nine (GON) tiles and bind GONs to GONs. The third, mediated by IIIa and VIII, binds each GOS to five surrounding GONs. Optimization of adenovirus for cancer and gene therapy could target these networks.
引用
收藏
页码:1038 / 1043
页数:6
相关论文
共 40 条
[1]   Insights into assembly from structural analysis of bacteriophage PRD1 [J].
Abrescia, NGA ;
Cockburn, JJB ;
Grimes, JM ;
Sutton, GC ;
Diprose, JM ;
Butcher, SJ ;
Fuller, SD ;
Martín, CS ;
Burnett, RM ;
Stuart, DI ;
Bamford, DH ;
Bamford, JKH .
NATURE, 2004, 432 (7013) :68-74
[2]  
Berk A.J., 2007, FIELDS VIROLOGY, VII, P2356
[3]   HUMAN ADENOVIRUS TYPE-2 PROTEIN-IIIA .2. MATURATION AND ENCAPSIDATION [J].
BOUDIN, ML ;
DHALLUIN, JC ;
COUSIN, C ;
BOULANGER, P .
VIROLOGY, 1980, 101 (01) :144-156
[5]   Membrane structure and interactions with protein and DNA in bacteriophage PRD1 [J].
Cockburn, JJB ;
Abrescia, NGA ;
Grimes, JM ;
Sutton, GC ;
Diprose, JM ;
Benevides, JM ;
Thomas, GJ ;
Bamford, JKH ;
Bamford, DH ;
Stuart, DI .
NATURE, 2004, 432 (7013) :122-125
[6]   ADENOVIRUS TYPE-5 VIRIONS CAN BE ASSEMBLED INVIVO IN THE ABSENCE OF DETECTABLE POLYPEPTIDE-IX [J].
COLBY, WW ;
SHENK, T .
JOURNAL OF VIROLOGY, 1981, 39 (03) :977-980
[7]  
CROWTHER R A, 1972, Journal of Molecular Biology, V68, P181, DOI 10.1016/0022-2836(72)90273-2
[8]   Direct visualization of the putative portal in the Kaposi's sarcoma-associated herpesvirus capsid by cryoelectron tomography [J].
Deng, Binbin ;
O'Connor, Christine M. ;
Kedes, Dean H. ;
Zhou, Z. Hong .
JOURNAL OF VIROLOGY, 2007, 81 (07) :3640-3644
[9]   STRUCTURAL PROTEINS OF ADENOVIRUSES .12. LOCATION AND NEIGHBOR RELATIONSHIP AMONG PROTEINS OF ADENOVIRION TYPE-2 AS REVEALED BY ENZYMATIC IODINATION, IMMUNOPRECIPITATION AND CHEMICAL CROSS-LINKING [J].
EVERITT, E ;
LUTTER, L ;
PHILIPSON, L .
VIROLOGY, 1975, 67 (01) :197-208
[10]  
Everts M, 2004, CURR GENE THER, V4, P337