Featured Research

from universities, journals, and other organizations

UCSD Discovery May Provide Novel Method To Generate Medically Useful Proteins

September 19, 2005
University of California - San Diego
A team led by UCSD biochemists has discovered the mechanism by which a simple organism can produce 10 trillion varieties of a single protein, a finding that provides a new tool to develop novel drugs.

Graphic shows molecular structure of predator protein variants (colors reveal different amino acids). Credit: Jason Miller, UCSD

Related Articles

In the September 18 advance on-line publication of thejournal Nature Structural and Molecular Biology, the researchersdescribe the mechanism by which a virus that infects bacteria—called abacteriophage, or phage—can generate a kaleidoscope of variants of aparticular protein. The paper will appear in print in Nature Structuraland Molecular Biology in October.

Since this degree of proteindiversity is extremely rare, recreating the process in a test tubecould give researchers a new way to generate therapeutic enzymes,vaccines and other medically important proteins.

“This is onlythe second type of massively variable protein ever discovered,”explained Partho Ghosh, a professor of chemistry and biochemistry atUCSD who headed the research team. “Only antibodies have more variationthan this protein in phage. However, the genetic mechanism used by thephage to generate this diversity is completely different from that usedby animals to produce antibodies, and has the advantage of giving theprotein greater stability.”

“If we can learn from these organismshow to set up a system that churns out proteins with enormousvariability, it may be possible to target these new proteins tospecific cells to treat disease,” said Stephen McMahon, a formerpostdoctoral fellow in Ghosh’s lab who conducted much of the research.“This idea has already been picked up by the biotech industry.”

Thefunction of the massively variable phage protein is to tether the phageto the bacteria they infect. The phage “predator” protein fits into a“prey” protein on the bacteria like a three-dimensional puzzle piece.However, the bacteria are constantly changing the proteins on theirsurface. To keep up with the unpredictable changes in the prey protein,the phage must generate many different predator proteins for at leastone to have an acceptable fit.

In their paper, the researchersdescribe how by altering the amino acids at one or more of just 12sites on the predator protein, the phage are able to generate 10trillion proteins, each with the potential to bind to a different preyprotein. This variability arises as DNA is being copied into the RNAblueprint for the protein. The sequence of DNA bases at the 12 siteshas unique characteristics that cause frequent mistakes to be made inthe copying process. As a result, the RNA ends up specifying adifferent amino acid, and a protein with different structural andchemical properties is created.

Antibodies are another typepredator protein that must respond to rapidly evolving prey proteins,because microorganisms are constantly altering proteins on theirsurfaces to evade the immune system. Unlike the phage protein,antibodies have a complicated loop structure. The size of the loopsvaries in addition to the amino acid building blocks that constitutethe antibody protein. Although this mechanism can generate more than100 trillion different antibodies, the researchers say replicating itin a test tube would be very challenging because the loops would havethe tendency to fold incorrectly.

“Because of its stability, thephage protein makes a better model to create protein diversity in atest tube,” explained Jason Miller, a graduate student in Ghosh’s labwho conducted much of the research. “Our discovery shows that naturehas provided at least two completely different methods to generate ahuge amount of protein variability, and it opens up a whole newplatform for protein development.”

Other contributors to thepaper were Jeffrey Lawton, Department of Chemistry, Eastern University;Donald Kerkow, The Scripps Research Institute; Marc Marti-Renom, EswarNarayanan, and Andrej Sali, Departments of Biopharmaceutical Sciencesand Pharmaceutical Chemistry, University of California, San Francisco;Asher Hodes, and Jeffrey Miller, Department of Microbiology,Immunology, and Molecular Genetics, David Geffen School of Medicine andthe Molecular Biology Institute, University of California, Los Angeles;and Sergei Doulatov, Department of Microbiology and Medical Genetics,University of Toronto.

Stephen McMahon is now at the Centre for Biomolecular Sciences at The University of St. Andrews in Scotland.

This research was supported by a W.M. Keck Distinguished Young Scholars in Medicine Award and a UC Discovery Grant.

Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.

Cite This Page:

University of California - San Diego. "UCSD Discovery May Provide Novel Method To Generate Medically Useful Proteins." ScienceDaily. ScienceDaily, 19 September 2005. <www.sciencedaily.com/releases/2005/09/050919081903.htm>.
University of California - San Diego. (2005, September 19). UCSD Discovery May Provide Novel Method To Generate Medically Useful Proteins. ScienceDaily. Retrieved January 25, 2015 from www.sciencedaily.com/releases/2005/09/050919081903.htm
University of California - San Diego. "UCSD Discovery May Provide Novel Method To Generate Medically Useful Proteins." ScienceDaily. www.sciencedaily.com/releases/2005/09/050919081903.htm (accessed January 25, 2015).

Share This

More From ScienceDaily

More Matter & Energy News

Sunday, January 25, 2015

Featured Research

from universities, journals, and other organizations

Featured Videos

from AP, Reuters, AFP, and other news services

NTSB: Missing Planes' Black Boxes Should Transmit Wirelessly

NTSB: Missing Planes' Black Boxes Should Transmit Wirelessly

Newsy (Jan. 23, 2015) In light of high-profile plane disappearances in the past year, the NTSB has called for changes to make finding missing aircraft easier. Video provided by Newsy
Powered by NewsLook.com
Iconic Metal Toy Meccano Goes Robotic

Iconic Metal Toy Meccano Goes Robotic

Reuters - Innovations Video Online (Jan. 22, 2015) Classic children&apos;s toy Meccano has gone digital, releasing a programmable kit robot that can be controlled by voice recognition. The toymakers say Meccanoid G15 KS is easy to use and is compatible with existing Meccano pieces. Jim Drury reports. Video provided by Reuters
Powered by NewsLook.com
The VueXL From VX1 Immersive Smartphone Headset!

The VueXL From VX1 Immersive Smartphone Headset!

Rumble (Jan. 22, 2015) The VueXL from VX1 is a product that you install your smartphone in and with the magic of magnification lenses, enlarges your smartphones screen so that it&apos;s like looking at a big screen TV. Check it out! Video provided by Rumble
Powered by NewsLook.com
Analysis: NTSB Wants Better Black Boxes

Analysis: NTSB Wants Better Black Boxes

AP (Jan. 22, 2015) NTSB investigators recommended Thursday that long-distance passenger planes carry improved technology to allow them to be found more easily in a crash, as well as include enhanced cockpit recording technology. (Jan. 22) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.


Breaking News:

Strange & Offbeat Stories

Space & Time

Matter & Energy

Computers & Math

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News


Free Subscriptions

Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile

Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?

Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins