dorsal/arxiv
View SchemaThe folding mechanics of a knotted protein
| Authors | Stefan Wallin, Konstantin B Zeldovich, Eugene I Shakhnovich |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0611073 |
| URL | https://arxiv.org/abs/q-bio/0611073 |
Abstract
An increasing number of proteins are being discovered with a remarkable and somewhat surprising feature, a knot in their native structures. How the polypeptide chain is able to knot itself during the folding process to form these highly intricate protein topologies is not known. Here, we perform a computational study on the 160-amino acid homodimeric protein YibK which, like other proteins in the SpoU family of MTases, contains a deep trefoil knot in its C-terminal region. In this study, we use a coarse-grained C-alpha-chain representation and Langevin dynamics to study folding kinetics. We find that specific, attractive nonnative interactions are critical for knot formation. In the absence of these interactions, i.e. in an energetics driven entirely by native interactions, knot formation is exceedingly unlikely. Further, we find, in concert with recent experimental data on YibK, two parallel folding pathways which we attribute to an early and a late formation of the trefoil knot, respectively. For both pathways, knot formation occurs before dimerization. A bioinformatics analysis of the SpoU family of proteins reveals further that the critical nonnative interactions may originate from evolutionary conserved hydrophobic segments around the knotted region.
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"abstract": "An increasing number of proteins are being discovered with a remarkable and\nsomewhat surprising feature, a knot in their native structures. How the\npolypeptide chain is able to knot itself during the folding process to form\nthese highly intricate protein topologies is not known. Here, we perform a\ncomputational study on the 160-amino acid homodimeric protein YibK which, like\nother proteins in the SpoU family of MTases, contains a deep trefoil knot in\nits C-terminal region. In this study, we use a coarse-grained C-alpha-chain\nrepresentation and Langevin dynamics to study folding kinetics. We find that\nspecific, attractive nonnative interactions are critical for knot formation. In\nthe absence of these interactions, i.e. in an energetics driven entirely by\nnative interactions, knot formation is exceedingly unlikely. Further, we find,\nin concert with recent experimental data on YibK, two parallel folding pathways\nwhich we attribute to an early and a late formation of the trefoil knot,\nrespectively. For both pathways, knot formation occurs before dimerization. A\nbioinformatics analysis of the SpoU family of proteins reveals further that the\ncritical nonnative interactions may originate from evolutionary conserved\nhydrophobic segments around the knotted region.",
"arxiv_id": "q-bio/0611073",
"authors": [
"Stefan Wallin",
"Konstantin B Zeldovich",
"Eugene I Shakhnovich"
],
"categories": [
"q-bio.BM"
],
"title": "The folding mechanics of a knotted protein",
"url": "https://arxiv.org/abs/q-bio/0611073"
},
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