Tue 06 Jan 2009
Adoration Of The Magi. Bartolomé Esteban Murillo (bapt. 1 Jan 1618 - 3 Apr 1682).
Off Tangent Comix
See our Annotated List of DSM-related news, research reports, analyses, and opinion pieces.
Visit the TS-Si Article Archive for reports on science, medicine, government, society, and other topics.
| Discovered: Key Component Of Quality Control In Human Cells |
 |
 |
| Science - Biological Sciences | |||
| TS-Si News Service | |||
| Thursday, 31 July 2008 17:00 | |||
  Protein folding is the physical process that results in the characteristic and functional 3-dimensional structure of a protein. [A]
An mRNA sequence is translated to a linear chain of amino acids. The result, a polypeptide, lacks a developed 3D structure (figure, left). However, acids in the chain have hydrophilic, hydrophobic, or electrically charged features that interact with each other and their cell surroundings. Their sequence determines details of the 3D structure that produce a well-defined shape known as the native state (figure, right, a folded protein). [B]
The correct 3D structure is essential for many proteins to function. [C] Failure to achieve the appropriate shape usually produces inactive proteins with different properties. Several neurodegenerative conditions and other diseases are believed to result from the accumulation of incorrectly folded (misfolded) proteins.
Protein misfolds are known to cause, at least in part, many well known diseases and neurological conditions. The list keeps growing: ALS, Alzheimer's, amyotrophic lateral sclerosis (ALS), bovine spongiform encephalopathy (BSE — Mad Cow), many Cancers and cancer-related syndromes, Creutzfeldt-Jakob disease (CJD), Huntington's, Parkinson's disease, and others.
Experimental determination of a protein's 3D structure is often very difficult and expensive. However, the sequence is often known, so scientists use different biophysical techniques for manual folding to predict the protein's structure. [A] The Shape and Structure of Proteins. Alberts, Bruce; Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walters (2002). Molecular Biology of the Cell; Fourth Edition. New York and London: Garland Science. ISBN 0-8153-3218-1.
[B] The formation and stabilization of protein structure. Anfinsen C (1972). Biochem. J. 128 (4): 737-49. PMID 4565129.
[C] Protein Structure and Function. Jeremy M. Berg, John L. Tymoczko, Lubert Stryer; Web content by Neil D. Clarke (2002). Biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-4684-0. The breakthrough occured while studying an enzme crucial to the development of cystic fibrosis (CF) and other hereditary diseases.
ERdj5 Is Required as a Disulfide Reductase for Degradation of Misfolded Proteins in the ER. Ryo Ushioda, Jun Hoseki, Kazutaka Araki, Gregor Jansen, David Y. Thomas, and Kazuhiro Nagata. Science 321(5888) 569-572. doi: 10.1126 / science.1159293
A key process in our bodies consists of protein formation. A gene provides a kind of blueprint that defines the precise sequence of amino acids necessary to make up a protein. The amino acids arrange in a linear (straight line) chain and form the proteins, which are comparatively large organic compounds.
[Technically, the chain of amino acids is joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid residues.]
However, this is not a specialty production process where each protein is prepared for shipment independent from all other proteins. The human body exploits economies of scale. In fact, our cells house a sophisticated stucture that is akin to a packaging plant. This is called the cell's endoplasmic reticulum (ER). It folds and prepares proteins for distribution inside or outside the cell.
Proteins can be misfolded in the ER; if so, they must be destroyed in a degradation process under control of the ERdj5 enzyme. The ERdj5 enzyme is the first protein found to be capable of breaking the disulfide bonds that hold the misfolded proteins together in the ER. Once those bonds are broken, the researchers say, ERdj5 also helps other enzymes and molecules break down the misfolded proteins completely so that the constituent amino acids can be recycled for further protein synthesis.
 Dr. David Thomas (McGill University) is Chair of Biochemistry and Canada Research Chair in Molecular Genetics. His team published their research findings in the journal Science.
The research team consisted of Dr. Kazahiro Nagata and colleagues at Kyoto University and the Japan Science Technology Agency (JST), and Dr. David Thomas and Dr. Gregor Jansen at McGill University in Montreal, Canada.
"ERdj5 is like a quality control inspector," says Thomas.
"If you ever owned an AMC Pacer and you now drive a BMW, you know the difference quality control can make. That's what ERdj5 does, it recognizes when a protein has 'manufacturing defects' and degrades it before it can be distributed."
"Unfortunately, the mechanism sometimes works a little too well," Dr. Thomas said. "It insists on BMW quality when a Honda would do. For example, some people carry a mutated version of the protein CFTR. The mutated protein is damaged but would still work fine if it were distributed, but in some individuals, the quality control mechanism insists on degrading it."
"It's the degradation of the protein, not the mutation itself, which causes cystic fibrosis. We're hoping this discovery will open up new avenues of research into treatments for CF."
 The TS-Si News Service is a collaborative effort by TS-Si.org editors, contributors, and corresponding institutions. The sources can include the cited individuals and organizations, as well as TS-Si.org staff contributions. Articles and news reports do not necessarily convey official positions of TS-Si, its partners, or affiliates. We welcome your comments. Use the form below to leave a public comment or send private correspondence via the TS-Si Contact Page. We will not divulge any personal details or place you on a mailing list without your permission.
Set as favorite
Bookmark
Email This
Comments (0)
 Write comment
|
|||
| Last Updated on Thursday, 31 July 2008 15:52 |
Subscribe to this comment's feed
Show/Hide comments
Show/Hide comment form
The TS-Si News Service is a collaboration of TS-Si staff, contributors, and corresponding institutions. Contents do not necessarily convey official positions of TS-Si, its partners, or affiliates.We welcome responsible comments. Use the public article forms throughout this site or send private correspondence via the TS-Si Contact Page. We will not divulge personal details or place you on a mailing list without your permission.
Except where noted, all works on this site are licensed under a Creative Commons Attribution-No Derivative Works 3.0 Unported License. Copyright © 2005-2009 TS-Si, Inc. Some rights reserved.