Structure and Mechanism of the CMR Complex for CRISPR-Mediated Antiviral Immunity

被引:238
作者
Zhang, Jing [3 ]
Rouillon, Christophe [3 ]
Kerou, Melina [3 ]
Reeks, Judith [3 ]
Brugger, Kim [4 ]
Graham, Shirley [3 ]
Reimann, Julia [5 ]
Cannone, Giuseppe [1 ,2 ]
Liu, Huanting [3 ]
Albers, Sonja-Verena [5 ]
Naismith, James H. [3 ]
Spagnolo, Laura [1 ,2 ]
White, Malcolm F. [3 ]
机构
[1] Univ Edinburgh, Inst Struct Mol Biol, Edinburgh EH9 3JR, Midlothian, Scotland
[2] Univ Edinburgh, Ctr Sci Extreme Condit, Edinburgh EH9 3JR, Midlothian, Scotland
[3] Univ St Andrews, St Andrews KY16 9ST, Fife, Scotland
[4] Univ Cambridge, Addenbrookes Hosp, EASIH, Cambridge CB2 0QQ, England
[5] Max Planck Inst Terr Microbiol, Archaeal Mol Biol Grp, D-35043 Marburg, Germany
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
STREPTOCOCCUS-THERMOPHILUS; HYPERTHERMOPHILIC ARCHAEON; SULFOLOBUS-SOLFATARICUS; DYNAMIC PROPERTIES; CAS SYSTEMS; RNA; DEFENSE; INTERFERENCE; RECOGNITION; EVOLUTION;
D O I
10.1016/j.molcel.2011.12.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The prokaryotic clusters of regularly interspaced palindromic repeats (CRISPR) system utilizes genomically encoded CRISPR RNA (crRNA), derived from invading viruses and incorporated into ribonucleoprotein complexes with CRISPR-associated (CAS) proteins, to target and degrade viral DNA or RNA on subsequent infection. RNA is targeted by the CMR complex. In Sulfolobus solfataricus, this complex is composed of seven CAS protein subunits (Cmr1-7) and carries a diverse "payload" of targeting crRNA. The crystal structure of Cmr7 and low-resolution structure of the complex are presented. S. solfataricus CMR cleaves RNA targets in an endo-nucleolytic reaction at UA dinucleotides. This activity is dependent on the 8 nt repeat-derived 5' sequence in the crRNA, but not on the presence of a proto-spacer-associated motif (PAM) in the target. Both target and guide RNAs can be cleaved, although a single molecule of guide RNA can support the degradation of multiple targets.
引用
收藏
页码:303 / 313
页数:11
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