Control of protein functional dynamics by peptide linkers. Export

@article{citeulike:2086854, abstract = {Control of structural flexibility is essential for the proper functioning of a large number of proteins and multiprotein complexes. At the residue level, such flexibility occurs due to local relaxation of peptide bond angles whose cumulative effect may result in large changes in the secondary, tertiary or quaternary structures of protein molecules. Such flexibility, and its absence, most often depends on the nature of interdomain linkages formed by oligopeptides. Both flexible and relatively rigid peptide linkers are found in many multidomain proteins. Linkers are thought to control favorable and unfavorable interactions between adjacent domains by means of variable softness furnished by their primary sequence. Large-scale structural heterogeneity of multidomain proteins and their complexes, facilitated by soft peptide linkers, is now seen as the norm rather than the exception. Biophysical discoveries as well as computational algorithms and databases have reshaped our understanding of the often spectacular biomolecular dynamics enabled by soft linkers. Absence of such motion, as in so-called molecular rulers, also has desirable functional effects in protein architecture. We review here the historic discovery and current understanding of the nature of domains and their linkers from a structural, computational, and biophysical point of view. A number of emerging applications, based on the current understanding of the structural properties of peptides, are presented in the context of domain fusion of synthetic multifunctional chimeric proteins.}, address = {School of Health Information Sciences and Institute of Molecular Medicine University of Texas, Health Science Center Houston, Houston, TX 77030, USA. wriggers@biomachina.org}, author = {Wriggers, Willy and Chakravarty, Sugoto and Jennings, Patricia A.}, citeulike-article-id = {2086854}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/bip.20291}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15880774}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15880774}, doi = {10.1002/bip.20291}, issn = {0006-3525}, journal = {Biopolymers}, keywords = {protein-domains, protein-dynamics}, number = {6}, pages = {736--746}, posted-at = {2009-07-31 09:01:01}, priority = {3}, title = {Control of protein functional dynamics by peptide linkers.}, url = {http://dx.doi.org/10.1002/bip.20291}, volume = {80}, year = {2005} }

TY - JOUR ID - citeulike:2086854 L3 - citeulike-article-id:2086854 N2 - Control of structural flexibility is essential for the proper functioning of a large number of proteins and multiprotein complexes. At the residue level, such flexibility occurs due to local relaxation of peptide bond angles whose cumulative effect may result in large changes in the secondary, tertiary or quaternary structures of protein molecules. Such flexibility, and its absence, most often depends on the nature of interdomain linkages formed by oligopeptides. Both flexible and relatively rigid peptide linkers are found in many multidomain proteins. Linkers are thought to control favorable and unfavorable interactions between adjacent domains by means of variable softness furnished by their primary sequence. Large-scale structural heterogeneity of multidomain proteins and their complexes, facilitated by soft peptide linkers, is now seen as the norm rather than the exception. Biophysical discoveries as well as computational algorithms and databases have reshaped our understanding of the often spectacular biomolecular dynamics enabled by soft linkers. Absence of such motion, as in so-called molecular rulers, also has desirable functional effects in protein architecture. We review here the historic discovery and current understanding of the nature of domains and their linkers from a structural, computational, and biophysical point of view. A number of emerging applications, based on the current understanding of the structural properties of peptides, are presented in the context of domain fusion of synthetic multifunctional chimeric proteins. IS - 6 JF - Biopolymers SN - 0006-3525 AD - School of Health Information Sciences and Institute of Molecular Medicine University of Texas, Health Science Center Houston, Houston, TX 77030, USA. wriggers@biomachina.org EP - 746 TI - Control of protein functional dynamics by peptide linkers. VL - 80 SP - 736 KW - protein-domains KW - protein-dynamics AU - Wriggers, Willy AU - Chakravarty, Sugoto AU - Jennings, Patricia PY - 2005/// UR - http://dx.doi.org/10.1002/bip.20291 ER -