Robustness and generalization of structure-based models for protein folding and function

Ribosomes translate mRNAs with non-uniform speed. Translation velocity patterns are a conserved feature of mRNA and have evolved to fine-tune protein folding, expression and function. Synonymous single-nucleotide polymorphisms (sSNPs) that alter programmed translational speed affect expression and function of the encoded protein. Synergistic advances in next-generation sequencing have led to the identification of sSNPs associated with disease penetrance. Here, we draw on studies with disease-related proteins to enhance our understanding of mechanistic contributions of sSNPs to functional alterations of the encoded protein. We emphasize the importance of identification of sSNPs along with disease-causing mutations to understand genotype–phenotype relationships.

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Chapter 17 Oxidant-specific protein folding during fungal oxidative stress: Activation and function of the yaplp transcription factor in Saccharomyces cerevisiae

Stress in Yeast and Filamentous Fungi - British Mycological Society Symposia Series ◽

10.1016/s0275-0287(08)80059-8 ◽

2008 ◽

pp. 275-290

Author(s):

W. Scott Moye-Rowley

Keyword(s):

Oxidative Stress ◽

Saccharomyces Cerevisiae ◽

Transcription Factor ◽

Protein Folding ◽

Specific Protein ◽

And Function ◽

Stress Activation

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3. Proteins

Biochemistry: A Very Short Introduction ◽

10.1093/actrade/9780198833871.003.0003 ◽

2021 ◽

pp. 34-51

Author(s):

Mark Lorch

Keyword(s):

Amino Acids ◽

Protein Folding ◽

Protein Structure ◽

Protein Structures ◽

Structure And Function ◽

Vast Array ◽

A Cell ◽

Cellular Machinery ◽

And Function ◽

The Relationship

This chapter examines proteins, the dominant proportion of cellular machinery, and the relationship between protein structure and function. The multitude of biological processes needed to keep cells functioning are managed in the organism or cell by a massive cohort of proteins, together known as the proteome. The twenty amino acids that make up the bulk of proteins produce the vast array of protein structures. However, amino acids alone do not provide quite enough chemical variety to complete all of the biochemical activity of a cell, so the chapter also explores post-translation modifications. It finishes by looking as some dynamic aspects of proteins, including enzyme kinetics and the protein folding problem.

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[1] Electrostatic effects in protein folding, stability, and function

Methods in Enzymology - Molecular Design and Modeling: Concepts and Applications Part A: Proteins, Peptides, and Enzymes ◽

10.1016/0076-6879(91)02003-r ◽

1991 ◽

pp. 3-19 ◽

Cited By ~ 11

Author(s):

N.M. Allewell ◽

H. Oberoi

Keyword(s):

Protein Folding ◽

Electrostatic Effects ◽

And Function

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Familial Parkinson's Disease-associated L166P Mutation Disrupts DJ-1 Protein Folding and Function

Journal of Biological Chemistry ◽

10.1074/jbc.m311017200 ◽

2003 ◽

Vol 279 (9) ◽

pp. 8506-8515 ◽

Cited By ~ 178

Author(s):

James A. Olzmann ◽

Keith Brown ◽

Keith D. Wilkinson ◽

Howard D. Rees ◽

Qing Huai ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protein Folding ◽

And Function ◽

Familial Parkinson’S Disease

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Design of self-assembling transmembrane helical bundles to elucidate principles required for membrane protein folding and ion transport

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0214 ◽

2017 ◽

Vol 372 (1726) ◽

pp. 20160214 ◽

Cited By ~ 12

Author(s):

Nathan H. Joh ◽

Gevorg Grigoryan ◽

Yibing Wu ◽

William F. DeGrado

Keyword(s):

Protein Folding ◽

Membrane Protein ◽

Protein Design ◽

De Novo ◽

Cell Signalling ◽

Membrane Protein Folding ◽

Cellular Processes ◽

Membrane Pores ◽

Self Assembling ◽

And Function

Ion transporters and channels are able to identify and act on specific substrates among myriads of ions and molecules critical to cellular processes, such as homeostasis, cell signalling, nutrient influx and drug efflux. Recently, we designed Rocker, a minimalist model for Zn 2+ /H + co-transport. The success of this effort suggests that de novo membrane protein design has now come of age so as to serve a key approach towards probing the determinants of membrane protein folding, assembly and function. Here, we review general principles that can be used to design membrane proteins, with particular reference to helical assemblies with transport function. We also provide new functional and NMR data that probe the dynamic mechanism of conduction through Rocker. This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.

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