Immunity system complexity: spotting attackers in bacterias (Introduction)

by David Turell , Friday, September 02, 2022, 19:40 (812 days ago) @ David Turell

A whole new mechanism is discovered:

https://www.quantamagazine.org/bacterias-immune-sensors-reveal-a-novel-way-to-detect-vi...

"All of the life forms on Earth have the same problem,” said Jonathan Kagan, an immunology researcher at Boston Children’s Hospital. “And that is dealing with infection.” Just as we worry about bacterial infections, bacteria are on the watch for the viruses called phages that infect them, and — like every organism across every kingdom of life — they have evolved an arsenal of molecular tools to fight infections.

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"Some of these antiviral defenses, such as CRISPR-Cas9, recognize specific sequences in the DNA that a phage injects into its host. Others don’t directly sense fragments of the virus but respond to evidence of the harm the virus causes, such as damaged DNA or malfunctioning cellular processes — the molecular equivalents of the broken glass at the scene of a break-in.

"...researchers led by Feng Zhang of the Massachusetts Institute of Technology and Eugene Koonin of the National Center for Biotechnology Information have now discovered. Avs proteins can directly detect viral proteins manufactured by the cell’s hijacked machinery.

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"Zhang’s group found that Avs proteins aren’t bothered by little changes in amino acid sequences — or by big ones, for that matter. “We tested 24 different phages, spanning nine phage families,” said Alex Gao, a biochemist at Stanford University and the lead author on the paper, “and found that there was almost this across-the-board activation” of Avs.

"The targeted proteins in the different viral families had almost completely different amino acid sequences, but they all performed the same job: spooling up strands of viral DNA and packing them into newly formed virus particles. Consequently, they all retained the same functional shape.

"Avs proteins take advantage of this molecular resemblance, the team realized. The proteins were “recognizing three-dimensional folds and shapes, rather than sequences,” Gao explained. An Avs protein “basically wraps like a glove around a hand.” This type of 3D structural recognition “doesn’t have a whole lot of precedent, as far as we know, in molecular biology,” he added."

Comment: An amazingly complex protein defense mechanism of which we apparently have a trace. It also reeks of design.

The only way for these viral proteins to escape Avs detection would be to mutate into an unrecognizable shape. But “to change the shape without destabilizing the protein or otherwise compromising its function in the phage is not trivial,” said Koonin.

The versatile, wraparound recognition skills of the Avs proteins aren’t limited to spotting viruses that infect bacteria. Koonin recalled asking Gao as a joke whether the Avs proteins could detect animal herpesviruses — very distant relatives of the phages tested in the paper. To his surprise, Gao responded, “‘Yes, we have already done that! They do.” Avs proteins recognized the DNA-packing proteins in human herpesviruses, although the recognition was weaker than for the bacterial phages.