Navigation Links
Many needles, many haystacks

Most of what happens in cells is the work of machines that contain dozens of molecules, chiefly proteins. With the completion of human and other genomes, researchers now have a nearly complete "parts list" of such machines; what's lacking now is the manual telling where all the pieces go. A new study by scientists at the European Molecular Biology Laboratory (EMBL) promises to answer this question for some of the smallest and trickiest components in the cellular toolbox. Their work appears in the current issue of the Public Library of Science's on-line journal, PLoS Biology.

A protein consists of a sticky string of amino acids which usually folds up because of attractions between some of its atoms. This creates a bundle called a globular domain whose shape and chemistry determine what other molecules can bind to it.

"If we could look at the chemical 'spelling' of a protein and guess what machines it fits into, we'd know a lot more about what happens in cells," says Rob Russell, head of the Heidelberg lab that carried out the current study. "We've made a lot of progress in predicting how globular domains interact with each other. But sometimes a surface on one globular domain will grab a tiny, string-like region of another protein called a linear motif. Finding such motifs and predicting where they fit in is like looking for needles in haystacks."

Or like looking at a line of automobiles and trying to decide which one a bulky motor fits into ?versus trying to find where a tiny screw goes. Linear motifs are so small that it is hard to tell what features allow them to bind to other molecules. Now Victor Neduva, a PhD student in Russell's group, has developed a method to scan molecules and tease out new linear motifs.

"If two or more different proteins share a binding partner, there is often a common motif," Neduva says. "The hard part is finding a 3-to-8 'letter' pattern in a protein sequence that may be thousands of amino acids long."The method Neduva and his colleagues invented draws on large-scale studies of protein binding in the cells of yeast, flies, worms and humans. Those studies have produced parts lists of molecular machines. And the data holds a wealth of information about linear motifs ?if it can be mined.

The scientists distilled all of this information in a series of steps ?discarding parts of the proteins likely to dock via large surfaces, and zooming in on small regions of the remaining molecules that might hold motifs. Then it was up to the computer to scan the sequences for small patterns. The attempt was successful: in the fly data, for example, 26 sets of proteins seemed to be interacting through linear motifs.

"One challenge was to eliminate red herrings, which crop up everywhere when you look for very small patterns," Russell says. "The fact that nine of these motifs were already known was a sign we were on the right trail; we then did follow-up experiments in collaboration with Luis Serrano's group at EMBL to test some of the others."

One prediction, for example, suggested that a linear motif would bind to the fly protein translin. The scientists verified that this happened, then they made subtle changes in the sequence. When these changes stopped the molecules binding, they knew they had a new linear motif.

Now the lab will expand the method; Russell predicts that hundreds of linear motifs remain to be discovered. This has important implications for the study of genetic diseases. "A lot of work has gone into discovering mutations that affect protein binding," he says. "Because linear motifs are so small, every bit of information is crucial, and any change is likely to be disruptive. But so far, because of their size, these motifs have been below the radar of most methods to tie protein structures to disease."


'"/>

Source:European Molecular Biology Laboratory


Related biology news :

1. Finding Cures For Tropical Diseases: Is Open Source An Answer?
2. Fundamental Finding Yields Insight into Stem Cells, Cancer; Opens Door to Drug Discovery
3. Findings have implications for tracking disease, drugs at the molecular level
4. Finding hidden invaders in a Hawaiian rain forest
5. New Finding May Aid Adult Stem Cell Collection
6. Finding the minds eye
7. Findings advance use of adult stem cells for replacement bone
8. Finding a virus is not all bad news
9. Finding a better way to make biodiesel
10. Finding paves way for better treatment of autoimmune disease
11. Finding the right mix: A biomaterial blend library
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/3/2017)... 3, 2017  Data captured by IsoCode, ... detected a statistically significant association between the ... treatment and objective response of cancer patients ... predict whether cancer patients will respond to ... well as to improve both pre-infusion potency testing ...
(Date:3/30/2017)... HONG KONG , March 30, 2017 ... developed a system for three-dimensional (3D) fingerprint identification by adopting ground ... technology into a new realm of speed and accuracy for use ... applications at an affordable cost. ... ...
(Date:3/29/2017)... , March 29, 2017  higi, the health ... in North America , today announced ... and the acquisition of EveryMove. The new investment and ... set of tools to transform population health activities through ... lifestyle data. higi collects and secures data ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... ComplianceOnline’s Medical Device Summit is ... and 8th June 2018 in San Francisco, CA. The Summit brings together current and ... distinguished CEOs, board directors and government officials from around the world to address key ...
(Date:10/11/2017)... ... 2017 , ... Disappearing forests and increased emissions are the main causes of ... year. Especially those living in larger cities are affected by air pollution related diseases. ... most pollution-affected countries globally - decided to take action. , “I knew I had ...
(Date:10/10/2017)... (PRWEB) , ... October 10, ... ... development-stage cancer-focused pharmaceutical company advancing targeted antibody-drug conjugate (ADC) therapeutics, today confirmed ... targeted HPLN (Hybrid Polymerized Liposomal Nanoparticle), a technology developed in collaboration with ...
(Date:10/10/2017)... SomaGenics announced the receipt of a Phase ... (Single Cell), expected to be the first commercially available ... from single cells using NGS methods. The NIH,s recent ... development of approaches to analyze the heterogeneity of cell ... for measuring levels of mRNAs in individual cells have ...
Breaking Biology Technology: