dorsal/arxiv
View SchemaEntropic stabilization of proteins and its proteomic consequences
| Authors | Igor N. Berezovsky, William W. Chen, Paul J. Choi, Eugene I. Shakhnovich |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0506032 |
| URL | https://arxiv.org/abs/q-bio/0506032 |
| DOI | 10.1371/journal.pcbi.0010047 |
Abstract
We report here a new entropic mechanism of protein thermostability due to residual dynamics of rotamer isomerization in native state. All-atom simulations show that Lysines have much greater number of accessible rotamers than Arginines in folded states of proteins. This finding suggests that Lysines would preferentially entropically stabilize the native state. Indeed we show in computational experiments that Arginine-to-Lysine amino acid substitutions result in noticeable stabilization of proteins. We then hypothesize that if evolution uses this physical mechanisms in its strategies of thermophilic adaptation then hyperthermostable organisms would have much greater content of Lysines in their proteomes than of comparable in size and similarly charged Arginines.. Consistent with that, high-throughput comparative analysis of complete proteomes shows extremely strong bias towards Arginine-to-Lysine replacement in hyperthermophilic organisms and overall much greater content of Lysines than Arginines in hyperthermophiles. This finding cannot be explained by GC compositional biases. Our study provides an example of how analysis of a delicate physical mechanism of thermostability helps to resolve a puzzle in comparative genomics as to why aminoacid compositions of hyperthermophilic proteomes are significantly biased towards Lysines but not Arginines
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"abstract": "We report here a new entropic mechanism of protein thermostability due to\nresidual dynamics of rotamer isomerization in native state. All-atom\nsimulations show that Lysines have much greater number of accessible rotamers\nthan Arginines in folded states of proteins. This finding suggests that Lysines\nwould preferentially entropically stabilize the native state. Indeed we show in\ncomputational experiments that Arginine-to-Lysine amino acid substitutions\nresult in noticeable stabilization of proteins. We then hypothesize that if\nevolution uses this physical mechanisms in its strategies of thermophilic\nadaptation then hyperthermostable organisms would have much greater content of\nLysines in their proteomes than of comparable in size and similarly charged\nArginines.. Consistent with that, high-throughput comparative analysis of\ncomplete proteomes shows extremely strong bias towards Arginine-to-Lysine\nreplacement in hyperthermophilic organisms and overall much greater content of\nLysines than Arginines in hyperthermophiles. This finding cannot be explained\nby GC compositional biases. Our study provides an example of how analysis of a\ndelicate physical mechanism of thermostability helps to resolve a puzzle in\ncomparative genomics as to why aminoacid compositions of hyperthermophilic\nproteomes are significantly biased towards Lysines but not Arginines",
"arxiv_id": "q-bio/0506032",
"authors": [
"Igor N. Berezovsky",
"William W. Chen",
"Paul J. Choi",
"Eugene I. Shakhnovich"
],
"categories": [
"q-bio.BM",
"cond-mat.soft",
"physics.bio-ph",
"q-bio.GN"
],
"doi": "10.1371/journal.pcbi.0010047",
"title": "Entropic stabilization of proteins and its proteomic consequences",
"url": "https://arxiv.org/abs/q-bio/0506032"
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