Navigation Links
UCSD discovery may provide novel method to generate medically useful proteins

A team led by University of California, San Diego 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.

In the September 18 advance on-line publication of the journal Nature Structural and Molecular Biology, the researchers describe the mechanism by which a virus that infects bacteria--called a bacteriophage, or phage--can generate a kaleidoscope of variants of a particular protein. The paper will appear in print in Nature Structural and Molecular Biology in October.

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

"This is only the second type of massively variable protein ever discovered," explained Partho Ghosh, a professor of chemistry and biochemistry at UCSD who headed the research team. "Only antibodies have more variation than this protein in phage. However, the genetic mechanism used by the phage to generate this diversity is completely different from that used by animals to produce antibodies, and has the advantage of giving the protein greater stability." "If we can learn from these organisms how to set up a system that churns out proteins with enormous variability, it may be possible to target these new proteins to specific cells to treat disease," said Stephen McMahon, a former postdoctoral fellow in Ghosh's lab who conducted much of the research. "This idea has already been picked up by the biotech industry."

The function of the massively variable phage protein is to tether the phage to 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 their surface. To keep up with the unpredictab le changes in the prey protein, the phage must generate many different predator proteins for at least one to have an acceptable fit.

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

Antibodies are another type predator protein that must respond to rapidly evolving prey proteins, because microorganisms are constantly altering proteins on their surfaces to evade the immune system. Unlike the phage protein, antibodies have a complicated loop structure. The size of the loops varies in addition to the amino acid building blocks that constitute the antibody protein. Although this mechanism can generate more than 100 trillion different antibodies, the researchers say replicating it in a test tube would be very challenging because the loops would have the tendency to fold incorrectly.

"Because of its stability, the phage protein makes a better model to create protein diversity in a test tube," explained Jason Miller, a graduate student in Ghosh's lab who conducted much of the research. "Our discovery shows that nature has provided at least two completely different methods to generate a huge amount of protein variability, and it opens up a whole new platform for protein development."

Other contributors to the paper were Jeffrey Lawton, Department of Chemistry, Eastern University; Donald Kerkow, The Scripps Research Institute; Marc Marti-Renom, Eswar Narayanan, and Andrej Sali, Department s of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California, San Francisco; Asher Hodes, and Jeffrey Miller, Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine and the 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.


'"/>

Source:University of California - San Diego


Related biology news :

1. Protein discovery could unlock the secret to better TB treatment
2. Purdue proves concept of using nano-materials for drug discovery
3. UCSD discovery may help extend life of natural pesticide
4. Leprosy microbes lead scientists to immune discovery
5. Biochemists report discovery of structure of major piece of telomerase; implications for cancer
6. Researchers make surprise discovery that some neurons can transmit three signals at once
7. Important discovery about second most fatal cancer
8. Harmless virus may hold key to more effective HIV drug discovery
9. Fundamental discovery -- Bone fracture
10. Genetic discovery could lead to drought-resistant plants
11. Gene discovery sheds light on causes of rare disease, cancer
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/23/2016)... March 23, 2016 ... Sicherheit Gesichts- und Stimmerkennung mit Passwörtern ... (NASDAQ: MESG ), ein führender Anbieter ... Unternehmen mit SpeechPro zusammenarbeitet, um erstmals dessen ... wird die Möglichkeit angeboten, im Rahmen mobiler ...
(Date:3/21/2016)... Unique technology combines v ... security   Xura, Inc. ... digital communications services, today announced it is working alongside ... customers, particularly those in the Financial Services Sector, the ... within a mobile app, alongside, and in combination with, ...
(Date:3/15/2016)... --> --> ... Research "Digital Door Lock Systems Market - Global Industry Analysis, ... global digital door lock systems market in terms of revenue ... forecast to grow at a CAGR of 31.8% during the ... enterprises (MSMEs) across the world and high industrial activity driving ...
Breaking Biology News(10 mins):
(Date:5/3/2016)... ... May 03, 2016 , ... According to world renowned prostate ... prostate cancer treatment, patients traditionally had two main treatment options: surgery or radiation. Based ... made. , New technology has enabled doctors to administer higher doses of ...
(Date:5/2/2016)... Q BioMed Inc. (QBIO), a ... Research Inc. will be attending the Association for Research ... May 1-5, 2016 in Seattle Washington ... vendors and research partners. The meeting provides organizations the ... collaborative opportunities for the MAN-01 program for treatment of ...
(Date:5/2/2016)... ... May 02, 2016 , ... StarNet Communications Corp, ( http://www.starnet.com/ ) ... of three Secure Remote Desktop modules to its flagship X-Win32 PC X server. ... Unix servers to the user’s PC over encrypted SSH. , Traditionally, users of PC ...
(Date:4/29/2016)... ... ... The MIT bioLogic design team has won multiple A' Design Awards ... applied to fabric and formed into living interfaces between body and environment. They found ... team harvested Natto cells and applied them to fabric with custom 3D printers.The cell-infused ...
Breaking Biology Technology: