The genius disorderly enzyme

The genius of a disorderly enzyme

11:48 AM, 30th June 2011
The genius of a disorderly enzyme

USC Dornsife researchers uncover how the inefficiency of activation-induced deoxycytidine deaminase is good for your immune system.

LOS ANGELES, US: Why is antibody diversity important? Think about it like this, said Myron Goodman: “Why don’t you die when I sneeze? It’s because you have a powerful immune system. And the way to get a decent immune system is for your body to have a way to respond to insults it has never seen before.”

Random patterns of deamination by the enzyme activation-induced deoxycytidine deaminase (AID) are the key to generating antibody diversity, a crucial component to a healthy immune system, according to a new study by USC Dornsife researchers published in The Journal of Biological Chemistry.

Having variation in the types of antibodies produced by your body gives it a fighting chance to respond to those “insults.” Antibodies protect against invasion by antigens such as bacteria or viruses by locating them in the body and neutralizing them.

To create antibody diversity, mutations must occur in the variable region of immunoglobulin genes, the region where antibodies bind to invaders. Generating those mutations has to be a really random process according to Goodman, Professor of Biological Sciences and Chemistry in USC Dornsife. This is where AID steps in.

Goodman and his colleagues monitored the actions of AID. The enzyme essentially moves back and forth along the DNA strand and sporadically deaminates, or converts, cytosine to uracil triggering a mutation in tri-nucleotide motifs - sequences comprising three bases - found along the DNA. They found that AID was extremely inefficient and initiated chemical reactions in favoured motifs only about 3 per cent of the time. By mutating the motifs so haphazardly, the researchers suggest that AID produces antibody diversity. Enzymes like AID that scan single-stranded DNA have been studied far less extensively than enzymes that scan double-stranded DNA.

“This is the first really clear picture of what AID is doing during the scanning process,” Goodman said.

Their paper, “An Analysis of a Single-stranded DNA Scanning Process in which AID Deaminates C to U Haphazardly and Inefficiently to Ensure Mutational Diversity” published online May 12, was selected by The Journal of Biological Chemistry as a “Paper of the Week” to appear in the July 15 print issue.

Authors on the paper are from USC Dornsife and include Phuong Pham, Assistant Professor (Research) of Biological Sciences; Calabrese, Assistant Professor (Research) of Biological Sciences; Goodman, Professor of Biological Sciences and Chemistry; and Soo Jung Park, Research Assistant. The National Institutes of Health funded the study.

(C) University of Southern California, Dornsife College News

 

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