Bacterial immunity; more on CAS enzymes (Introduction)

by David Turell , Friday, November 30, 2018, 00:05 (1980 days ago) @ David Turell

This is part of the CRISPR enzyme system that scientists have converted to use for slicing up DNA and tailoring it for study. This study shows how bacteria use it for immune protection:

https://phys.org/news/2018-11-shape-shifting-protein-bacteria-invaders.html

"The study, published in Molecular Cell, shows that the protein Cas10 is usually harmless, but transforms into an enzymatic assassin when confronted with foreign genetic material.

"One way that bacteria protect themselves is through the use of CRISPRs, or clustered regularly interspaced short palindromic repeats, and associated Cas proteins. These systems not only fend off pathogens, but also memorize them: when a bacterium is attacked, it copies and stores a section of the invader's DNA. This genetic sequence, called a spacer, helps the bacterium identify the invader next time it strikes. Once a trespasser is detected, Cas enzymes dissolve its DNA.

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"In 2017, Marraffini and his colleagues showed that Type III systems have the unique ability to target not just a single invader sequence, but variations on a genetic theme. This means that even if a virus mutates, CRISPR-Cas can still identify and destroy its DNA.

"'For other systems, you have a single mutation in the target sequence and immunity is usually lost," says Liu. "But type III systems, which use the Cas10 enzyme, can be effective even when the target has multiple mutations."

"Compared to enzymes in other CRISPR types, Cas10 fires at relatively wide variety of targets; yet, it manages to avoid harming a bacteria's own DNA. How, Liu wondered, do type III complexes discriminate between self and other?

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"The researchers found that when Cas10 was exposed to an invader's RNA, the enzyme's structure took on new shapes. And, Liu says, as Cas10 cycles through various conformations, it intermittently enters active states, which imbue the enzyme with DNA-dissolving powers.

"By contrast, when then Cas10 encountered "self" RNA, the enzyme became locked in an inactive position, which prohibited any dicing and slicing of DNA. These results, says Liu, explain how type III systems avoid self-destructive behavior.

"'We don't want Cas10 to go around randomly cleaving DNA. Its activity has to be regulated," he says. "And it appears that the enzyme is operative only when it is unlocked from its inactive configuration."

Read more at: https://phys.org/news/2018-11-shape-shifting-protein-bacteria-invaders.html#jCp

"The researchers also found that when Cas10 was exposed to mutated enemy RNA, the enzyme could bend into only a limited number active shapes. And as the malleability of Cas10 decreased, so did the strength of the bacterium's immune response.

"These findings suggest that a robust immune response depends on Cas10's ability to move around: When the enzyme can shimmy freely, it spends more time in an active state, and thus more time degrading dangerous DNA. Still, Liu notes, even when the enzyme loses some of its flexibility, it does not entirely forfeit its ability to injure invaders."

Comment: If this process of a shape-altering enzyme was fully known, it would help answer the dhw/David debate about automaticity in cells: does the CAS10 simply react on its own in changing its form or can a directive process be found. That directive process can also be automatic or shown to be an independent control. At some point as layers are plied off the answer will appear.

Read more at: https://phys.org/news/2018-11-shape-shifting-protein-bacteria-invaders.html#jCp

Read more at: https://phys.org/news/2018-11-shape-shifting-protein-bacteria-invaders.html#jCp