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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
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Source:European Molecular Biology Laboratory


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