Structure and Disorder: Protein Functions Depend on This New Binary Transforming Lock-and-key Into Structure-function Continuum
Document Type
Book Chapter
Publication Date
2023
Keywords
Structure-function Paradigm, Central Dogma, Lock-and-key, Induced Fit, Proteoform, Intrinsic Disorder, Intrinsically Disordered Protein, Intrinsically Disordered Region, Protein–protein Interactions, Posttranslational Modifications
Digital Object Identifier (DOI)
https://doi.org/10.1016/B978-0-323-99533-7.00008-X
Abstract
Recent developments in the field of protein science indicated that the classical “lock-and-key” and “induced fit” models cannot adequately describe protein multifunctionality and binding promiscuity, which are important phenomena defining the dramatic increase in the size of a functional proteome in comparison with the size of a corresponding genome. In fact, introduction of the proteoform concept, where a single gene produces a multitude of highly related, but chemically different protein molecules due to the various events at the DNA (genetic variations), mRNA (alternative splicing, alternative promoter usage, alternative initiation of translation, and mRNA editing), and protein levels (posttranslational modifications), provides only a partial solution to these problems. Based on the currently accumulated knowledge, a more thorough solution requires complementation of these induced proteoforms with the intrinsic conformational proteoforms generated via the presence of intrinsically disordered or structurally flexible regions in a protein and functioning proteoforms originating from the functionality-induced changes in the conformational ensembles of both intrinsic and induced proteoforms. Therefore a single gene encodes not one unique protein but a wide array of structurally and functionally different proteoforms. In other words, since a given protein exists as a dynamic conformational ensemble containing multiple structurally and functionally different proteoforms, the protein multifunctionality is rooted in the “protein structure-function continuum” model.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Structure and Disorder: Protein Functions Depend on This New Binary Transforming Lock-and-key Into Structure-function Continuum, in M. N. Gupta & V. N. Uversky (Eds.), Structure and Intrinsic Disorder in Enzymology, Academic Press, p. 127-148
Scholar Commons Citation
Gupta, Munishwar Nath and Uversky, Vladimir N., "Structure and Disorder: Protein Functions Depend on This New Binary Transforming Lock-and-key Into Structure-function Continuum" (2023). Molecular Medicine Faculty Publications. 1121.
https://digitalcommons.usf.edu/mme_facpub/1121
