Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins Export

@article{citeulike:1298516, abstract = {10.1073/pnas.0700329104 Transcription factors and other allosteric cell signaling proteins contain a disproportionate number of domains or segments that are intrinsically disordered (ID) under native conditions. In many cases folding of these segments is coupled to binding with one or more of their interaction partners, suggesting that intrinsic disorder plays an important functional role. Despite numerous hypotheses for the role of ID domains in regulation, a mechanistic model has yet to be established that can quantitatively assess the importance of intrinsic disorder for intramolecular site-to-site communication, the hallmark property of allosteric proteins. Here, we present such a model and show that site-to-site allosteric coupling is maximized when intrinsic disorder is present in the domains or segments containing one or both of the coupled binding sites. This result not only explains the prevalence of ID domains in regulatory proteins, it also calls into question the classical mechanical view of energy propagation in proteins, which predicts that site-to-site coupling would be maximized when a well defined pathway of folded structure connects the two sites. Furthermore, in showing that the coupling mechanism conferred by intrinsic disorder is robust and independent of the network of interactions that physically link the coupled sites, unique insights are gained into the energetic ground rules that govern site-to-site communication in all proteins.}, address = {Department of Biochemistry and Molecular Biology, and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555-1068.}, author = {Hilser, Vincent J. and Thompson, E. Brad}, citeulike-article-id = {1298516}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0700329104}, citeulike-linkout-1 = {http://www.pnas.org/content/104/20/8311.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/104/20/8311.full.pdf}, citeulike-linkout-3 = {http://www.pnas.org/cgi/content/abstract/104/20/8311}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/17494761}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=17494761}, day = {15}, doi = {10.1073/pnas.0700329104}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, keywords = {41061161, mechanism, optimize, proteins}, month = {May}, number = {20}, pages = {8311--8315}, posted-at = {2007-05-16 21:29:46}, priority = {3}, title = {Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins}, url = {http://dx.doi.org/10.1073/pnas.0700329104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:1298516 L3 - citeulike-article-id:1298516 N2 - 10.1073/pnas.0700329104 Transcription factors and other allosteric cell signaling proteins contain a disproportionate number of domains or segments that are intrinsically disordered (ID) under native conditions. In many cases folding of these segments is coupled to binding with one or more of their interaction partners, suggesting that intrinsic disorder plays an important functional role. Despite numerous hypotheses for the role of ID domains in regulation, a mechanistic model has yet to be established that can quantitatively assess the importance of intrinsic disorder for intramolecular site-to-site communication, the hallmark property of allosteric proteins. Here, we present such a model and show that site-to-site allosteric coupling is maximized when intrinsic disorder is present in the domains or segments containing one or both of the coupled binding sites. This result not only explains the prevalence of ID domains in regulatory proteins, it also calls into question the classical mechanical view of energy propagation in proteins, which predicts that site-to-site coupling would be maximized when a well defined pathway of folded structure connects the two sites. Furthermore, in showing that the coupling mechanism conferred by intrinsic disorder is robust and independent of the network of interactions that physically link the coupled sites, unique insights are gained into the energetic ground rules that govern site-to-site communication in all proteins. IS - 20 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 AD - Department of Biochemistry and Molecular Biology, and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555-1068. EP - 8315 TI - Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins VL - 104 SP - 8311 KW - 41061161 KW - mechanism KW - optimize KW - proteins AU - Hilser, Vincent AU - Thompson, Brad PY - 2007/05/15/ UR - http://dx.doi.org/10.1073/pnas.0700329104 ER -