Navigation Links
Disorderly enzyme is key for antibody diversity

Los Angeles, Calif. (June 27, 2011) Why is antibody diversity important? Think about it like this, said Myron Goodman, who is an author on the paper: "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 researchers at the USC Dana and David Dornsife College of Letters, Arts and Sciences. The paper, "An Analysis of a Single-stranded DNA Scanning Process in which AID Deaminates C to U Haphazardly and Inefficiently to Ensure Mutational Diversity," was 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 do that, antibodies must bind to antigens. The more variation in the types of antibodies produced by the body, the more likely they will be able to bind to and fight off antigens, which come in many forms.

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 as it scanned single-stranded DNA or transcribed double-stranded DNA. 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.

Unlike most enzymes that are exquisitely efficient in targeting favored motifs, they found that AID was extremely inefficient. AID initiated chemical reactions in favored motifs only about 3 percent of the time. By mutating the motifs so haphazardly, the researchers suggest that AID produces antibody diversity.

The study also sheds light on a little-studied group of enzymes. Enzymes such as 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.

To identify and describe AID's complex process during scanning, the team used a genetic assay to measure the distribution of AID-induced mutations on individual DNA molecules and then analyzed the mutational data computationally using a random walk model, developed for the study by USC Dornsife researcher Peter Calabrese. By combining the genetic and computational analyses, they were able to calculate the distribution of mutations that occurred with a remarkable fit to their experimental data. The fit entailed matching theory to experiment for the patterns of closely spaced mutations and separately for the distances between mutated and non-mutated target motifs.


Contact: Michelle Salzman
University of Southern California

Related medicine news :

1. New Delhi metallo-beta-lactamase-1 enzyme acquired in Canada
2. Enzyme may drive breast cancer growth
3. Study suggests enzyme crucial to DNA replication may provide potent anti-cancer drug target
4. The TET1 enzyme steers us through fetal development and fights cancer
5. Investigators discover enzyme essential for healthy lung development
6. Newly discovered role for enzyme in neurodegenerative diseases
7. Enzyme helps prepare lung tissue for metastatic development
8. Heart Enzymes May Predict Outcome After Bypass Surgery
9. Breathing easy: LSU biochemists offer first 3-D model of asthma-causing inflammation enzyme
10. Princess Margaret Hospital researchers identify a key enzyme that affects radiation response
11. Chaperone enzyme provides new target for cancer treatments
Post Your Comments:
(Date:11/30/2015)... ... November 30, 2015 , ... Olympic Gold Medalists and Celebrity ... brands across various categories through traditional and social media marketing campaigns and other ... of Gold Medal Moms who can connect with today’s most important consumer: mothers. ...
(Date:11/30/2015)... ... December 01, 2015 , ... The ... a 2015-2016 inductee into its VIP Woman of the Year Circle. She is ... leading networking organization exclusively for professional women, boasting 850,000 members and over 200 ...
(Date:11/30/2015)... , ... November 30, 2015 , ... ... (Meso Foundation) released information for caregivers and held two webinars on topics of ... on demand free of charge at . , With a loved ...
(Date:11/30/2015)... ... November 30, 2015 , ... MOSI recently added two state-of-the-art augmented reality (AR) ... the Jurassic to their collection of interactive exhibits within the Kids In Charge! building. ... allow guests to get closer than ever to a range of animals as they ...
(Date:11/30/2015)... VA (PRWEB) , ... November 30, 2015 , ... ... mesothelioma-affected community across the United States to access life-saving information provided ... Malignant Mesothelioma will consist of three individual conferences in three major cities: ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... , Nov. 30, 2015  QT Vascular Ltd., ... and together with its subsidiaries, TriReme Medical LLC and ... company engaged in the design, assembly and distribution of ... vascular disease, is pleased to announce that a three-judge ... Court of Appeals for the Federal Circuit ("Federal Circuit") ...
(Date:11/30/2015)... 2015   Royal Philips  (NYSE: PHG ... Radiology Solutions, a fully integrated, consultative approach to ... data-driven practice management approaches that combine imaging systems, ... improve care delivery and reduce costs. Making its ... North America Annual Meeting (RSNA) in ...
(Date:11/30/2015)... -- Nautilus Medical Inc. today announced worldwide availability of ... ). The release of MatrixRay to the entire medical ... North America) in Chicago - ... --> --> MatrixRay is the ... studies worldwide via a peer-to-peer exchange network of physicians ...
Breaking Medicine Technology: