Snowy Owl
Retired in 2010, In Memoriam
Researchers Provide Evidence of How Proteins Fold
http://www.newswise.com/articles/view/523162/?sc=dwhp
http://www.newswise.com/articles/view/523162/?sc=dwhp
Source: Cornell University
Description
Experimental evidence provided by a Cornell University researcher and colleagues at the Scripps Research Institute in La Jolla, Calif., support a long-held theory of how and where proteins fold to create their characteristic shapes and biological functions.
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</td> </tr> </tbody></table> <!--</form>--> </td> </tr> </tbody></table> </td> </tr><tr> </tr></tbody></table> Newswise ? Experimental evidence provided by a Cornell researcher and colleagues at the Scripps Research Institute in La Jolla, Calif., support a long-held theory of how and where proteins fold to create their characteristic shapes and biological functions.
The theory proposes that proteins start to fold in specific places along an amino acid chain (called a polypeptide chain) that contains nonpolar groups, or groups of molecules without a charge, and continue to fold by aggregation, i.e., as several individuals of these nonpolar groupings combine. Using the same principle that separates oil and water, these molecules are hydrophobic -- they avoid water and associate with each other.
In the water-based cell fluid, where long polypeptide chains are manufactured and released by ribosomes, the polypeptide chains rapidly fold up into their biologically functional structure. The theory proposes that there are sites along the polypeptide chains where hydrophobic groups initially fold in on themselves, creating small nonpolar (hydrophobic) pockets that are protected from the water.
"What drives this polypeptide chain to fold up?" asked Harold Scheraga, professor emeritus of chemistry and chemical biology at Cornell and a co-author of a paper published in the Aug. 29 issue of the Proceedings of the National Academy of Sciences (and already available online). "That has been the subject of my investigations for some time, and the cited experimental verification of the theory provides a sound basis for further computational work to identify the specific steps in the folding pathway.
"Protein folding is a frontier problem in protein chemistry," said Scheraga, noting that an ability to predict how and where proteins fold could lead to understanding such protein misfolding diseases as Alzheimer's and cystic fibrosis, designing drugs that act on proteins and even creating designer proteins with new functions.
The theory is based on two methods to show that initial folding sites occur among nonpolar groups in a polypeptide chain. Lead author H. Jane Dyson and Peter Wright, both professors of molecular biology at the Scripps Research Institute, used an experimental nuclear magnetic resonance procedure to validate the predicted results of the two theoretical methods.
The first method used supercomputers to calculate the energy required to convert a polypeptide chain into a collapsed hydrophobic pocket. The folds occur in several places that require the least possible energy to maintain.
By finding these places where the nonpolar groups exist, the researchers better understand where folding occurs along a linear polypeptide chain.
The second method involved mapping a folded protein by tracing the folding steps required to arrive at the protein's native structure. This method mapped three stages of folding. First, the short-range contacts between amino acids that are very close to each other were mapped, revealing the initial nonpolar (hydrophobic) folds. The next two stages show folds that occur between points that are farther from each other along the polypeptide chain. These secondary folds may attach two or three hydrophobic pockets.
These two methods were used together in this study to pinpoint where on a polypeptide chain the nonpolar segments occur and where initial folding takes place and then propagates to the final folded form.
Experimental evidence provided by a Cornell University researcher and colleagues at the Scripps Research Institute in La Jolla, Calif., support a long-held theory of how and where proteins fold to create their characteristic shapes and biological functions.
<script language="JavaScript" type="text/javascript"> <!-- // swap href in links // accepts two parameters: href of link calling swap(), and the new url to // swap with. // ============================== // Set the following variables... // ============================== // Set the slideshow speed (in milliseconds) var SlideShowSpeed = 3000; // Set the duration of crossfade (in seconds) var CrossFadeDuration = 2; var Picture = new Array(); // don't change this var Caption = new Array(); // don't change this var Credit = new Array(); // don't change this var Imagelink = new Array(); // don't change this var Imagenumber = new Array(); // don't change this var showHot = false; // don't change this // Specify the image files... // To add more images, just continue // the pattern, adding to the array below. // To use fewer images, remove lines // starting at the end of the Picture array. // Caution: The number of Pictures *must* // equal the number of Captions! Picture[1] = 'http://www.newswise.com/images/uploads/2006/08/31/thumbs/protein_folding.jpg'; // Specify the Captions... // To add more captions, just continue // the pattern, adding to the array below. // To use fewer captions, remove lines // starting at the end of the Caption array. // Caution: The number of Captions *must* // equal the number of Pictures! //Caption[1] = "This is the first caption."; //Caption[2] = "This is the second caption."; Caption[1] = 'This illustration shows a designed protein transformed from an unfolded into a folded form.'; Credit[1] = 'Adam Liwo'; Imagelink[1] = 'http://www.newswise.com/images/uploads/2006/08/31/fullsize/protein_folding.jpg'; Imagenumber[1] = '<center>Image 1 of 1</center>'; // ===================================== // Do not edit anything below this line! // ===================================== var tss; var iss; var jss = 1; var pss = Picture.length-1; var isOpera = 0;var preLoad = new Array(); for (iss = 1; iss < pss+1; iss++){ preLoad[iss] = new Image(); preLoad[iss].src = Picture[iss];} function control(how){ if (showHot){ var prevjss = jss; if (how=="H") jss = 1; if (how=="F") jss = jss + 1; if (how=="B") jss = jss - 1; if (jss > (pss)) jss=1; if (jss < 1) jss = pss; swap(Imagelink[prevjss], Imagelink[jss]); if (document.all && isOpera == 0){ document.images.PictureBox.style.filter="blendTrans(duration=2)"; document.images.PictureBox.style.filter="blendTrans(duration=CrossFadeDuration)"; document.images.PictureBox.filters.blendTrans.Apply();} document.images.PictureBox.src = preLoad[jss].src; if (document.getElementById) document.getElementById("ImageNumber").innerHTML= Imagenumber[jss]; if (document.getElementById) document.getElementById("CaptionBox").innerHTML= Caption[jss]; if (document.getElementById) document.getElementById("CreditBox").innerHTML= Credit[jss]; if (document.all && isOpera == 0) document.images.PictureBox.filters.blendTrans.Play(); }} function swap(swapHref, newHref) { var docLinks = new Array(); for (i=0; i < document.links.length; i++) { docLinks = document.links.href; // alert(docLinks); } for (i=0; i<docLinks.length; i++) { if (docLinks == swapHref) { document.links.href = newHref; // alert(newHref); } } } // --> </script> <table style="padding-left: 15px; padding-bottom: 15px;" align="right" border="0" cellspacing="0"> <tbody><tr> <td> <table style="border: 1px solid rgb(204, 204, 204); background-color: rgb(238, 238, 238);" align="right" border="0" cellpadding="10" cellspacing="0"> <tbody><tr> <!-- The next table cell holds the images. Set cell and image width and height the same. The img src must have name=PictureBox in its tag. Often, the first image in the Picture array in the script is used here; but you may also use a different, introductory image as we have here, since this image is shown only on start-up. --> <td style="padding: 8px; vertical-align: middle;" colspan="3"> <center> <table style="border: 1px solid rgb(153, 153, 153); background-color: rgb(255, 255, 255); width: 330px; height: 330px;" border="0" cellpadding="10" cellspacing="0"> <tbody><tr> <td> <center>
</center> Adam Liwo
</td> </tr> <tr> <!-- The next table cell holds the captions. This table cell must have id=CaptionBox and class=Caption in its tag. The default caption shows whilst loading in all browsers; NS4 will show only the default caption, throughout. --> <td id="CaptionBox" class="Caption" align="center"> This illustration shows a designed protein transformed from an unfolded into a folded form. </td> </tr> </tbody></table> </center> </td> </tr> <!-- The following three cells contain the controls. Each of the control a href's must contain class= Controls, to attach the styles (see top of script). To dress this up a bit, you can of course substitute img src images for the text in the links. --> <!--| | |--> <tr> <td colspan="3" align="center" valign="top"> <!--<form name="noform" action="/" method="post" enctype="multipart/form-data">--> <table border="0" cellpadding="0" cellspacing="0" width="100%"> <tbody><tr> <td align="center" valign="top"></td> <td id="ImageNumber" class="Imagenum" align="center" valign="middle">Image 1 of 1</td> <td align="center" valign="top"> </td> </tr> </tbody></table> <!--</form>--> </td> </tr> </tbody></table> </td> </tr><tr> </tr></tbody></table> Newswise ? Experimental evidence provided by a Cornell researcher and colleagues at the Scripps Research Institute in La Jolla, Calif., support a long-held theory of how and where proteins fold to create their characteristic shapes and biological functions.The theory proposes that proteins start to fold in specific places along an amino acid chain (called a polypeptide chain) that contains nonpolar groups, or groups of molecules without a charge, and continue to fold by aggregation, i.e., as several individuals of these nonpolar groupings combine. Using the same principle that separates oil and water, these molecules are hydrophobic -- they avoid water and associate with each other.
In the water-based cell fluid, where long polypeptide chains are manufactured and released by ribosomes, the polypeptide chains rapidly fold up into their biologically functional structure. The theory proposes that there are sites along the polypeptide chains where hydrophobic groups initially fold in on themselves, creating small nonpolar (hydrophobic) pockets that are protected from the water.
"What drives this polypeptide chain to fold up?" asked Harold Scheraga, professor emeritus of chemistry and chemical biology at Cornell and a co-author of a paper published in the Aug. 29 issue of the Proceedings of the National Academy of Sciences (and already available online). "That has been the subject of my investigations for some time, and the cited experimental verification of the theory provides a sound basis for further computational work to identify the specific steps in the folding pathway.
"Protein folding is a frontier problem in protein chemistry," said Scheraga, noting that an ability to predict how and where proteins fold could lead to understanding such protein misfolding diseases as Alzheimer's and cystic fibrosis, designing drugs that act on proteins and even creating designer proteins with new functions.
The theory is based on two methods to show that initial folding sites occur among nonpolar groups in a polypeptide chain. Lead author H. Jane Dyson and Peter Wright, both professors of molecular biology at the Scripps Research Institute, used an experimental nuclear magnetic resonance procedure to validate the predicted results of the two theoretical methods.
The first method used supercomputers to calculate the energy required to convert a polypeptide chain into a collapsed hydrophobic pocket. The folds occur in several places that require the least possible energy to maintain.
By finding these places where the nonpolar groups exist, the researchers better understand where folding occurs along a linear polypeptide chain.
The second method involved mapping a folded protein by tracing the folding steps required to arrive at the protein's native structure. This method mapped three stages of folding. First, the short-range contacts between amino acids that are very close to each other were mapped, revealing the initial nonpolar (hydrophobic) folds. The next two stages show folds that occur between points that are farther from each other along the polypeptide chain. These secondary folds may attach two or three hydrophobic pockets.
These two methods were used together in this study to pinpoint where on a polypeptide chain the nonpolar segments occur and where initial folding takes place and then propagates to the final folded form.
