Welcome!

News Feed Item

The Ultimate Decoy: Scripps Research Institute Scientists Find Protein that Misdirects Immune System

LA JOLLA, Calif., Feb. 6, 2014 /PRNewswire-USNewswire/ -- A team led by scientists at The Scripps Research Institute (TSRI) has discovered an unusual bacterial protein that attaches to virtually any antibody and prevents it from binding to its target. Protein M, as it is called, probably helps some bacteria evade the immune response and establish long-term infections.

If follow-up studies confirm Protein M's ability to defeat the antibody response, it is likely to become a target of new antibacterial therapies. The protein's unique ability to bind generally to antibodies also should make it a valuable tool for research and drug development.

"What Protein M does to antibodies represents a very clever trick of evolution," said Richard A. Lerner, MD, Lita Annenberg Hazen Professor of Immunochemistry and Institute Professor at TSRI who led the research.

The new findings, which were achieved through collaboration among several laboratories at TSRI and elsewhere, are described in the February 7, 2014 issue of the journal Science.

Unexpected Discovery

The unexpected discovery originated from an effort to understand the origin of multiple myeloma, a B-cell carcinoma. Clonal B-cell proliferation, as well as lymphomas and myelomas, can result from chronic infections by organisms such as Escherichia coli (E. coli), Helicobacter pylori (H. pylori) and hepatitis C virus.

To better understand this process, the team investigated mycoplasma, a parasite that infects people chronically and is largely confined to the surface of cells. In a search for factors associated with long-term mycoplasma infection, Rajesh Grover, PhD, a senior staff scientist in the Lerner laboratory, tested samples of antibodies from multiple myeloma patients' blood against a variety of mycoplasma species. One of the proteins recognized by the antibodies was from Mycoplasma genitalium, which causes sexually transmitted infections in humans.

To the scientists' surprise, every antibody sample tested showed reactivity to this protein. But further tests made clear that these antibody reactions were not in response to mass infection with M. genitalium. Instead, the scientists found, the mysterious M. genitalium protein appeared to have evolved simply to bind to any antibody it encounters.

That presents a potentially major problem for the immune system. The antibody response is meant to combat invading pathogens with precisely targeted attacks, each selected from an enormous repertoire of hundreds of millions of distinct antibodies. In effect, the system is designed not to bind universally to any one target. If it did, then such a target could act as a universal decoy, potentially nullifying the entire antibody response.

The current research suggested that M. genitalium has evolved such a decoy. "It binds to every antibody generically—capable of hijacking the entire diversity of antibody repertoire—but at the same time it blocks the specific interaction between that antibody and its intended biomolecular target," said Grover.

'Protein M'

The team decided to call it "Protein M."

To better how understand Protein M works, Xueyong Zhu, PhD, a staff scientist in the laboratory of Ian Wilson, DPhil, Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI, and colleagues took a structural biology approach. Using X-ray crystallography and other techniques, including electron microscopy in the TSRI lab of Assistant Professor Andrew Ward, PhD, the team determined the protein's 3D atomic structure while the protein was bound to various human antibodies.

Compared to thousands of known structures in the Protein Data Bank, the worldwide structure database, Protein M appeared to be unique.

The data also revealed that Protein M binds to a small, unchanging—"conserved"—region at the outer tip of every antibody's antigen-binding arm. "It likely extends the other end of itself, like a tail, over the antibody's main antigen-binding region," Zhu said.

The team is now studying Protein M's function during M. genitalium infections. It seems likely that the oddball protein evolved to help M. genitalium cope with the immune response despite having one of the smallest bacterial genomes in nature. "It appears to represent an elegant evolutionary solution to the special problem that mycoplasma have in evading the adaptive immune system," said Grover. "The smallest parasitic bacteria on planet earth seems to have evolved the most sophisticated invading molecular machine."

Unusual—and Unusually Useful

If Protein M is confirmed as a universal decoy for antibodies, it will become a target for new drugs, which could make it easier to treat chronic, sometimes silent infections by M. genitalium and by any other microbes that have evolved a similar antibody-thwarting defense. Chronic infections can lead to a host of other problems, including inflammatory diseases and cancers.

In principle, Protein M also could be engineered to target specific groups of B cells—immune cells that produce antibodies and express them on their surfaces. Thus, Protein M could deliver cell-killing toxins to cancerous B cells but not healthy ones, for example to treat certain lymphomas.

In the era of antibody-based drugs, the most immediate use of Protein M is likely to be as a tool for grabbing antibodies in test tubes and cell cultures, useful for the preparation of highly pure antibody for research and drug manufacturing. Other generic antibody-binding proteins have been put to use in this way, but so far it appears that none does the job quite as well as Protein M. "It may be the most useful antibody purification device ever found," said Lerner, who is already in talks with industry to commercialize the protein.

In addition to Lerner, Wilson, Grover and Zhu, authors of the study, "A Structurally Unique Human Mycoplasma Protein that Generically Blocks Antigen-Antibody Union," were TSRI's Travis Nieusma, Teresa Jones, Isabel Boreo, Amanda S. MacLeod, Adam Mark, Sherry Niessen, Helen J. Kim, Leopold Kong, Vaughn V. Smider, Daniel R. Salomon and Andrew B. Ward; Nacyra Assad-Garcia, Keehwan Kwon and John I. Glass of the J Craig Venter Research Institute in Rockville, MD; Marta Chesi of the Mayo Clinic Arizona; Diane F. Jelinek and Robert A. Kyle of the Mayo Clinic College of Medicine in Rochester, MN; and Richard B. Pyles of the University of Texas Medical Branch, Galveston, TX.

The study was funded in part by the National Institutes of Health (RO1 AI042266, R21 AI098057, R01 AG020686, K08 AR063729, RR017573, U19 AI06360).

SOURCE The Scripps Research Institute

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
SYS-CON Events announced today that Juniper Networks (NYSE: JNPR), an industry leader in automated, scalable and secure networks, will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. Juniper Networks challenges the status quo with products, solutions and services that transform the economics of networking. The company co-innovates with customers and partners to deliver automated, scalable and secure network...
Deep learning has been very successful in social sciences and specially areas where there is a lot of data. Trading is another field that can be viewed as social science with a lot of data. With the advent of Deep Learning and Big Data technologies for efficient computation, we are finally able to use the same methods in investment management as we would in face recognition or in making chat-bots. In his session at 20th Cloud Expo, Gaurav Chakravorty, co-founder and Head of Strategy Development ...
DevOps is often described as a combination of technology and culture. Without both, DevOps isn't complete. However, applying the culture to outdated technology is a recipe for disaster; as response times grow and connections between teams are delayed by technology, the culture will die. A Nutanix Enterprise Cloud has many benefits that provide the needed base for a true DevOps paradigm. In his Day 3 Keynote at 20th Cloud Expo, Chris Brown, a Solutions Marketing Manager at Nutanix, will explore t...
Imagine having the ability to leverage all of your current technology and to be able to compose it into one resource pool. Now imagine, as your business grows, not having to deploy a complete new appliance to scale your infrastructure. Also imagine a true multi-cloud capability that allows live migration without any modification between cloud environments regardless of whether that cloud is your private cloud or your public AWS, Azure or Google instance. Now think of a world that is not locked i...
Technology innovation is the driving force behind modern business and enterprises must respond by increasing the speed and efficiency of software delivery. The challenge is that existing enterprise applications are expensive to develop and difficult to modernize. This often results in what Gartner calls "Bimodal IT," where business struggle to apply modern tools and practices to traditional monolithic applications. But these existing assets can be modernized and made more efficient without havin...
Most companies are adopting or evaluating container technology - Docker in particular - to speed up application deployment, drive down cost, ease management and make application delivery more flexible overall. As with most new architectures, this dream takes a lot of work to become a reality. Even when you do get your application componentized enough and packaged properly, there are still challenges for DevOps teams to making the shift to continuous delivery and achieving that reduction in cost...
SYS-CON Events announced today that SoftLayer, an IBM Company, has been named “Gold Sponsor” of SYS-CON's 18th Cloud Expo, which will take place on June 7-9, 2016, at the Javits Center in New York, New York. SoftLayer, an IBM Company, provides cloud infrastructure as a service from a growing number of data centers and network points of presence around the world. SoftLayer’s customers range from Web startups to global enterprises.
SYS-CON Events announced today that Auditwerx will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. Auditwerx specializes in SOC 1, SOC 2, and SOC 3 attestation services throughout the U.S. and Canada. As a division of Carr, Riggs & Ingram (CRI), one of the top 20 largest CPA firms nationally, you can expect the resources, skills, and experience of a much larger firm combined with the accessibility and attent...
SYS-CON Events announced today that Technologic Systems Inc., an embedded systems solutions company, will exhibit at SYS-CON's @ThingsExpo, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. Technologic Systems is an embedded systems company with headquarters in Fountain Hills, Arizona. They have been in business for 32 years, helping more than 8,000 OEM customers and building over a hundred COTS products that have never been discontinued. Technologic Systems’ pr...
SYS-CON Events announced today that CA Technologies has been named “Platinum Sponsor” of SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY, and the 21st International Cloud Expo®, which will take place October 31-November 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. CA Technologies helps customers succeed in a future where every business – from apparel to energy – is being rewritten by software. From ...
SYS-CON Events announced today that HTBase will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. HTBase (Gartner 2016 Cool Vendor) delivers a Composable IT infrastructure solution architected for agility and increased efficiency. It turns compute, storage, and fabric into fluid pools of resources that are easily composed and re-composed to meet each application’s needs. With HTBase, companies can quickly prov...
SYS-CON Events announced today that Loom Systems will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. Founded in 2015, Loom Systems delivers an advanced AI solution to predict and prevent problems in the digital business. Loom stands alone in the industry as an AI analysis platform requiring no prior math knowledge from operators, leveraging the existing staff to succeed in the digital era. With offices in S...
In his session at Cloud Expo, Alan Winters, an entertainment executive/TV producer turned serial entrepreneur, will present a success story of an entrepreneur who has both suffered through and benefited from offshore development across multiple businesses: The smart choice, or how to select the right offshore development partner Warning signs, or how to minimize chances of making the wrong choice Collaboration, or how to establish the most effective work processes Budget control, or how to max...
What if you could build a web application that could support true web-scale traffic without having to ever provision or manage a single server? Sounds magical, and it is! In his session at 20th Cloud Expo, Chris Munns, Senior Developer Advocate for Serverless Applications at Amazon Web Services, will show how to build a serverless website that scales automatically using services like AWS Lambda, Amazon API Gateway, and Amazon S3. We will review several frameworks that can help you build serverle...
MongoDB Atlas leverages VPC peering for AWS, a service that allows multiple VPC networks to interact. This includes VPCs that belong to other AWS account holders. By performing cross account VPC peering, users ensure networks that host and communicate their data are secure. In his session at 20th Cloud Expo, Jay Gordon, a Developer Advocate at MongoDB, will explain how to properly architect your VPC using existing AWS tools and then peer with your MongoDB Atlas cluster. He'll discuss the secur...