Structure and mechanism of the CMR complex for CRISPR-mediated antiviral immunity.
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 endonucleolytic 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 protospacer-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.
Biomedical Sciences Research Complex, University of St Andrews, Fife KY16 9ST, UK.
Jing
J
Zhang
Christophe
C
Rouillon
Melina
M
Kerou
Judith
J
Reeks
Kim
K
Brugger
Shirley
S
Graham
Julia
J
Reimann
Giuseppe
G
Cannone
Huanting
H
Liu
Sonja-Verena
SV
Albers
James H
JH
Naismith
Laura
L
Spagnolo
Malcolm F
MF
White
D019843:Archaeal Proteins / Q000737:chemistry* / Q000302:isolation & purification; D023641:Archaeal Viruses / Q000276:immunology; D001483:Base Sequence; D018360:Crystallography, X-Ray; D055029:Inverted Repeat Sequences; D046911:Macromolecular Substances / Q000737:chemistry / Q000302:isolation & purification; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000302:isolation & purification; D059367:RNA Cleavage; D019642:RNA, Archaeal / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D048229:Sulfolobus solfataricus / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000821:virology
D019843:Archaeal Proteins; D046911:Macromolecular Substances; D021122:Protein Subunits; D019642:RNA, Archaeal