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Understanding how proteins function in isolation and in their native context requires a merging of molecular-level techniques that explore the interplay of protein structure and dynamics.
Intrinsically disordered proteins (IDPs) are subject to ubiquitin-independent degradation, a default and passive process. We describe here a model wherein a group of 'nanny' proteins function to protect newly synthesized IDPs from degradation by default, thereby insuring their maturation into important regulatory molecules.
In their native environments, proteins perform their biological roles in highly concentrated viscous solutions and in complex networks with numerous partners. Yet for many years, the normal practice has been to purify a protein of interest in order to characterize its structural and functional properties. In this Commentary, we discuss how protein scientists are now tackling the theoretical and methodological challenges of studying proteins in their physiological context.
Phenotypic diversity exists even within isogenic populations of cells. Such nongenetic individuality may have wide implications for our understanding of many biological processes. The field of study concerned with the investigation of nongenetic individuality, also known as the 'biology of noise', is ripe with exciting scientific opportunities and challenges.
Building on a century of enzymology research and new genome-wide insights into enzyme families, increased interdisciplinary communication and a broad vision will advance our understanding of biological catalysts and enhance our ability to manipulate them.
Annotations of enzyme function provide critical starting points for generating and testing biological hypotheses, but the quality of functional annotations is hindered by uncertain assignments for uncharacterized sequences and by the relative sparseness of validated experimental data. Given the relentless increase in genomic data, new thinking and validation methods are urgently needed to provide high confidence in enzyme functional assignments.
The scope of enzymology has expanded rapidly over the last century, from an early focus on the chemical and catalytic mechanisms of individual enzymes to more recent efforts to understand enzyme action in the context of dynamic, functional biological systems consisting of many interacting enzymes and proteins. Continuing progress in probing the link between molecular structure and function now promises to pave the way for a deeper understanding of the evolution and behavior of the complex biological systems that govern cellular behavior.
Protein improvement strategies today involve widely varying combinations of rational design with random mutagenesis and screening. To make further progress—defined as making subsequent protein engineering problems easier to solve—protein engineers must critically compare these strategies and eliminate less effective ones.
