Abstract:
:Numerous experiments demonstrate a high level of promiscuity and structural disorder in organismal proteomes. Here, we ask the question what makes a protein promiscuous, that is, prone to nonspecific interactions, and structurally disordered. We predict that multi-scale correlations of amino acid positions within protein sequences statistically enhance the propensity for promiscuous intra- and inter-protein binding. We show that sequence correlations between amino acids of the same type are statistically enhanced in structurally disordered proteins and in hubs of organismal proteomes. We also show that structurally disordered proteins possess a significantly higher degree of sequence order than structurally ordered proteins. We develop an analytical theory for this effect and predict the robustness of our conclusions with respect to the amino acid composition and the form of the microscopic potential between the interacting sequences. Our findings have implications for understanding molecular mechanisms of protein aggregation diseases induced by the extension of sequence repeats.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Afek A,Shakhnovich EI,Lukatsky DBdoi
10.1016/j.jmb.2011.03.056subject
Has Abstractpub_date
2011-06-10 00:00:00pages
439-49issue
3eissn
0022-2836issn
1089-8638pii
S0022-2836(11)00345-7journal_volume
409pub_type
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