Protein Folding in the Cell (Campbell Biology)
Biochemists now know the amino acid sequence for about 65 million proteins, with roughly 1.5 million added each month, and the three-dimensional shape for almost 35,000. Researchers have tried to correlate the primary structure of many proteins with their three-dimensional structure to discover the rules of protein folding. Unfortunately, however, the protein-folding process is not that simple. Most proteins probably go through several intermediate structures on their way to a stable shape, and looking at the mature structure does not reveal the stages of folding required to achieve that form. However, biochemists have developed methods for tracking a protein through such stages and learning more about this important process.
Misfolding of polypeptides in cells is a serious problem that has come under increasing scrutiny by medical researchers. Many diseases—such as cystic fibrosis, Alzheimer’s, Parkinson’s, and mad cow disease—are associated with an accumulation of misfolded proteins. In fact, misfolded versions of the transthyretin protein have been implicated in several diseases, including one form of senile dementia.
Even when scientists have a correctly folded protein in hand, determining its exact three-dimensional structure is not simple, for a single protein has thousands of atoms. The method most commonly used to determine the 3-D structure of a protein is X-ray crystallography, which depends on the diffraction of an X-ray beam by the atoms of a crystallized molecule. Using this technique, scientists can build a 3-D model that shows the exact position of every atom in a protein molecule. Nuclear magnetic resonance (NMR) spectroscopy and bioinformatics (see Concept 5.6) are complementary approaches to understanding protein structure and function.
The structure of some proteins is difficult to determine for a simple reason: A growing body of biochemical research has revealed that a significant number of proteins, or regions of proteins, do not have a distinct 3-D structure until they interact with a target protein or other molecule. Their flexibility and indefinite structure are important for their function, which may require binding with different targets at different times. These proteins, which may account for 20–30% of mammalian proteins, are called intrinsically disordered proteins and are the focus of current research.
Urry, Lisa A.. Campbell Biology. Pearson Education. Kindle Edition. https://www.pearson.com/us/higher-education/series/Campbell-Biology-Series/2244849.html
Date Published: December 1, 2014 Publisher: Public Library of Science Author(s): Minghao Guo, Hannah Gelman, Martin Gruebele, Yaakov Koby Levy. http://doi.org/10.1371/journal.pone.0113040 Abstract: When a protein unfolds in the cell, its diffusion coefficient is affected by its increased hydrodynamic radius and by interactions of exposed hydrophobic residues with the cytoplasmic matrix, including chaperones. We characterize protein … Continue reading
Date Published: September 4, 2013 Publisher: Public Library of Science Author(s): Miguel A. Soler, Patrícia F. N. Faísca, Emanuele Paci. http://doi.org/10.1371/journal.pone.0074755 Abstract: This work explores the impact of knots, knot depth and motif of the threading terminus in protein folding properties (kinetics, thermodynamics and mechanism) via extensive Monte Carlo simulations of lattice models. A knotted … Continue reading
Date Published: April 12, 2013 Publisher: Public Library of Science Author(s): Shachi Gosavi, Yaakov Koby Levy. http://doi.org/10.1371/journal.pone.0061222 Abstract: When an amino-acid sequence cannot be optimized for both folding and function, folding can get compromised in favor of function. To understand this tradeoff better, we devise a novel method for extracting the “function-less” folding-motif of a protein … Continue reading
Date Published: January 17, 2013 Publisher: Public Library of Science Author(s): Cédric Debès, Minglei Wang, Gustavo Caetano-Anollés, Frauke Gräter, Ruth Nussinov Abstract: Nature has shaped the make up of proteins since their appearance, 3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be … Continue reading
Date Published: September 16, 2010 Publisher: Public Library of Science Author(s): Sergei V. Krivov, Jin Wang Abstract: Protein folding dynamics is often described as diffusion on a free energy surface considered as a function of one or few reaction coordinates. However, a growing number of experiments and models show that, when projected onto a reaction … Continue reading