Download or read book Investigation of Folding Stability and Function of Alpha Helical Membrane Proteins Under Native Condition written by Ruiqiong Guo and published by . This book was released on 2018 with total page 164 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Uncovering Membrane Protein Stability Under Native Conditions written by Robert Jefferson and published by . This book was released on 2016 with total page 139 pages. Available in PDF, EPUB and Kindle. Book excerpt: Membrane proteins are a neglected, but important class of proteins throughout the biological world. They carry out critical roles in the cell due to their unique location, such as transport across a membrane, transduction of exterior signals, and interaction between discrete aqueous regions. Despite the importance of these proteins, understanding of how they fold has lagged far behind that of soluble proteins. One of the primary challenges to studying membrane protein folding is developing methods that interrogate folding in the native environment of the lipid bilayer. Our lab has developed a method for measuring membrane protein stability under native conditions using a secondary protein that preferentially binds the unfolded state, obviating the need for harsh denaturants. Employing this method with a multimeric polytopic membrane protein, we measured an extremely slow unfolding rate, demonstrating that -helical membrane proteins can have high kinetic stability under non-denaturing conditions. Efforts were made to expand the steric trap method for single-molecule fluorescence measurements in lipid vesicles, but were ultimately stymied by the inability to preserve the trapped complexes for measurement. Our lab has also applied single-molecule techniques to membrane protein folding. We were able to map the energy landscape of a membrane protein in a lipid bilayer using forced unfolding driven by magnetic tweezers. Further advancements to this technique simplified the attachment chemistry to ready the protein for tweezing. These techniques can be applied to a wide array of membrane proteins in a broad spectrum of membrane environments.
Download or read book Membrane Protein Folding written by Derek Ng and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Protein Folding written by Charis Ghelis and published by Academic Press. This book was released on 2012-12-02 with total page 580 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein Folding aims to collect the most important information in the field of protein folding and probes the main principles that govern formation of the three-dimensional structure of a protein from a nascent polypeptide chain, as well as how the functional properties appear. This text is organized into three sections and consists of 15 chapters. After an introductory chapter where the main problems of protein folding are considered at the cellular level in the context of protein biosynthesis, the discussion turns to the conformation of native globular proteins. Definitions and rules of nomenclature are given, including the structural organization of globular proteins deduced from X-ray crystallographic data. Folding mechanisms are tentatively deduced from the observation of invariants in the architecture of folded proteins. The next chapters focus on the energetics of protein conformation and structure, indicating the principles of thermodynamic stability of the native structure, along with theoretical computation studies of protein folding, structure prediction, and folding simulation. The reader is also introduced to various experimental approaches; the reversibility of the unfolding-folding process; equilibrium and kinetic studies; and detection and characterization of intermediates in protein folding. This text concludes with a chapter dealing with problems specific to oligomeric proteins. This book is intended for research scientists, specialists, biochemists, and students of biochemistry and biology.
Download or read book The Protein Folding Problem written by Donald B Wetlaufer and published by Routledge. This book was released on 2019-06-21 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins in living systems carry out a great variety of specific functions, each of which depends on the precise three-dimensional structure of a particular protein. Proteins are synthesized in the form of a flexible polypeptide chain that is capable of assuming a vast number of configurations; the transformation of this chain into a specific, relatively rigid three-dimensional structure is called folding--a remarkable process of self-organization. It is known that the amino acid sequences of some proteins have sufficient information to determine their three-dimensional structures. There are other proteins whose folding requires additional information beyond that found in the sequence of the mature protein. This book introduces the central problem of folding mechanisms as well as a number of other closely related issues. This book is neither a textbook nor a treatise. Rather, it is an attempt by several investigators to convey the excitement and challenges of those aspects of the folding problem in which they are actively engaged. The contributors give brief introductions to protein folding from the perspectives of molecular architecture, stability and dynamics, phage genetics, DNA exons, general physiology, and natural selection. They point out emerging new directions, including the suggestion of a class of diseases that result from protein folding defects.
Download or read book Protein Folding written by Grace E. Orellana and published by American Chemical Society. This book was released on 2024-05-08 with total page 170 pages. Available in PDF, EPUB and Kindle. Book excerpt: Life as we know it would not exist if proteins did not fold into functional three-dimensional structures, where α-helices, loops, and β-sheets act together to form active sites that drive a myriad of biochemical reactions in the cell. The failure of this process is linked to the pathology of various diseases, such as neurodegenerative disorders like Alzheimer’s, genetic conditions (like cystic fibrosis), and cancer. It is no wonder that close to $2 billion in worldwide research funding has been devoted over the last five years (2019–2025) to helping scientists understand the molecular details of protein folding, how it can fail in ways that promote disease in humans, and clinical paths to treat or prevent diseases linked to protein misfolding. This primer is prerequisite reading to the literature on this important topic for readers new to the field. Chapter one provides exposure to the three-dimensional structure of proteins; readers will learn how to identify secondary structures, protein motifs, and domains involved in biological function. Chapter two introduces methodologies to determine the three-dimensional structure of proteins; readers will learn modern techniques to determine the secondary structure composition and the orientation of atoms in three-dimensional space. By providing exposure to how the physical environment (i.e., chemical denaturants, pH, pressure, and temperature) controls protein denaturation, readers will learn how such information can be used to study the biophysical characteristics of proteins through various probes and methodologies.
Download or read book Protein Folding written by Alka Dwevedi and published by Springer. This book was released on 2014-12-01 with total page 61 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book will discuss classes of proteins and their folding, as well as the involvement of bioinformatics in solving the protein folding problem. In vivo and in vitro folding mechanisms are examined, as well as the failures of in vitro folding, a mechanism helpful in understanding disease caused by misfolding. The role of energy landscapes is also discussed and the computational approaches to these landscapes.
Download or read book Investigation of the Role of Subdomains in Protein Folding and Misfolding written by Manuel Llinás and published by . This book was released on 1999 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Lipids in Protein Misfolding written by Olga Gursky and published by Springer. This book was released on 2015-07-06 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein conversion from a water-soluble native conformation to the insoluble aggregates and fibrils, which can deposit in amyloid plaques, underlies more than 20 human diseases, representing a major public health problem and a scientific challenge. Such a conversion is called protein misfolding. Protein misfolding can also involve errors in the topology of the folded proteins and their assembly in lipid membranes. Lipids are found in nearly all amyloid deposits in vivo, and can critically influence protein misfolding in vitro and in vivo in many different ways. This book focuses on recent advances in our understanding of the role of lipids in modulating the misfolding of various proteins. The main emphasis is on the basic biophysical studies that address molecular basis of protein misfolding and amyloid formation, and the role of lipids in this complex process.
Download or read book Misbehaving Proteins written by Regina Murphy and published by Springer Science & Business Media. This book was released on 2007-10-12 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: This text provides an up-to-date collection of theoretical and experimental studies into protein folding, misfolding, aggregation, and stability. Additionally, issues faced during the development of protein products are illustrated. It contains an introductory chapter for readers new to the protein folding field. The book provides a thorough and clear discussion of computational approaches to understanding and modeling protein aggregation.
Download or read book Experimental and Computational Studies on Protein Folding Misfolding and Stability written by Yun Wei and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins need fold to perform their biological function. Thus, understanding how proteins fold could be the key to understanding life. In the first study, the stability and structure of several [beta]-hairpin peptide variants derived from the C-terminus of the B1 domain of protein G (PGB1) were investigated by a number of experimental and computational techniques. Our analysis shows that the structure and stability of this hairpin can be greatly affected by one or a few simple mutations. For example, removing an unfavorable charge near the N-terminus of the peptide (Glu42 to Gln or Thr) or optimization of the N-terminal charge-charge interactions (Gly41 to Lys) both stabilize the peptide, even in water. Furthermore, a simple replacement of a charged residue in the turn (Asp47 to Ala) changes the [beta]-turn conformation. Our results indicate that the structure and stability of this [beta]-hairpin peptide can be modulated in numerous ways and thus contributes towards a more complete understanding of this important model [beta]-hairpin as well as to the folding and stability of larger peptides and proteins. The second study revealed that PGB1 and its variants can form amyloid fibrils in vitro under certain conditions and these fibrils resemble those from other proteins that have been implicated in diseases. To gain a further understanding of molecular mechanism of PGB1 amyloid formation, we designed a set of variants with mutations that change the local secondary structure propensity in PGB1, but have similar global conformational stability. The kinetics of amyloid formation of all these variants have been studied and compared. Our results show that different locations of even a single mutation can have a dramatic effect on PGB1 amyloid formation, which is in sharp contrast with a previous report. Our results also suggest that the [alpha]-helix in PGB1 plays an important role in the amyloid formation process of PGB1. In the final study, we investigate the forces that contribute to protein stability in a very general manner. Based on what we have learned about the major forces that contribute to the stability of globular proteins, protein stability should increase as the size of the protein increases. This is not observed: the conformational stability of globular proteins is independent of protein size. In an effort to understand why large proteins are not more stable than small proteins, twenty single-domain globular proteins ranging in size from 35 to 470 residues have been analyzed. Our study shows that nature buries more charged groups and more non-hydrogen-bonded polar groups to destabilize large proteins.
Download or read book Identification and Analysis of the Folding Determinants of Membrane Proteins written by Fiona Cunningham and published by . This book was released on 2011 with total page 414 pages. Available in PDF, EPUB and Kindle. Book excerpt: Membrane proteins are responsible for a variety of key cellular functions including transport of essential substrates across the membrane, signal transduction, and maintenance of cellular morphology. However, given the size and high hydrophobicity of membrane proteins, along with demanding expression and solubilization protocols that often preclude biophysical studies, novel approaches must be devised for studies of their structure and function. This thesis addresses these issues through several sets of inter-related experiments. We first examine sequence motifs directing alpha-helix packing, wherein the determinants of glycophorin A (GpA) dimerization were identified via TOXCAT assay and the evaluation of GpA-derived peptides. We found that (i) conservative mutations can have significant effects on the oligomerization of glycophorin A; and (ii) residues that introduce more efficiently packed structures that are poorly solvated by lipid leads to improved transmembrane segment dimerization. In a further study, we inquired into the criteria for selection of membrane-spanning alpha-helices by cellular machinery through investigation of hydrophobic helical segments (termed delta-helices) that we identified in soluble proteins. We found that the number and location of charged residues in a given hydrophobic helix are related to their insertion propensity as membrane-spanning segments. When we applied this criterion to delta-helices in their intact protein structures, we successfully determined the extent of delta-helix mutations necessary to convert a soluble protein, in part, to a membrane-inserted protein. Finally, using a three-transmembrane segment construct from the cystic fibrosis transmembrane conductance regulator (CFTR), we performed experiments aimed at optimizing criteria for protein overexpression, including construct design, choice of expression system, growth media, and expression temperature. The overall findings are interpreted in terms of progress towards defining the fundamental characteristics of membrane-spanning alpha-helices - from their primary amino acid sequence to the helix-helix interactions they display in the assembly of biologically-functional membrane protein structures.
Download or read book Membrane Protein Assembly written by Gunnar von Heijne and published by R. G. Landes. This book was released on 1997 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Physics of Amphiphilic Layers written by Jacques Meunier and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: Amphiphilic layers play essential roles in the behaviour of a great variety of disperse systems such as micelles, microemulsions and vesicles. They can also exist as isolated mono- or bilayers, or constitute extended liquid crystalline structures. Although the properties of these different systems may at first sight seem unrelated, theoretical interpretations of them depend on several common concepts. This was the reason for bringing together scientists working in this area for the International Winter School on the Physics of Amphiphilic Layers, which was held at Les Houches, 10-18 February, 1987. The topics treated in the proceedings volume are mono- and bilayers, interactive forces between layers (with special emphasis on steric forces), ordered structures (in particular swollen lamellar phases and defects), vesicles, micelles (including polymer-like systems), microemulsions (especially random bicontinuous structures) and porous media. The importance of thermal fluctuations in the amphiphilic layers is stressed. Recent results are presented and literature references allow readers not familiar with the subject to find any background information they require.
Download or read book Protein Folding Dynamics and Stability written by Prakash Saudagar and published by Springer Nature. This book was released on 2023-05-27 with total page 287 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes recent important advancements in protein folding dynamics and stability research, as well as explaining fundamentals and examining potential methodological approaches in protein science. In vitro, in silico, and in vivo method based research of how the stability and folding of proteins help regulate the cellular dynamics and impact cell function that are crucial in explaining various physiological and pathological processes. This book offers a comprehensive coverage on various techniques and related recent developments in the experimental and computational methods of protein folding, dynamics, and stability studies. The book is also structured in such a way as to summarize the latest developments in the fiddle and key concepts to ensure that readers can understand advanced concepts as well as the fundamental big picture. And most of all, fresh insights are provided into the convergence of protein science and technology. Protein Folding Dynamics and Stability is an ideal guide to the field that will be of value for all levels of researchers and advanced graduate students with training in biochemical laboratory research.
Download or read book Protein Folding written by C. M. Dobson and published by Cambridge University Press. This book was released on 1995 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: Discusses the molecular mechanisms controlling protein folding in vivo and in vitro.
Download or read book Protein Stability and Folding written by Wolfgang Pfeil and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 662 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein folding remains one of the most exclusive problems of modern biochemistry. Structure analysis has given access to the wealth of the molecular architecture of pro teins. As architecture needs static calculations, protein structure is always related to thermodynamic factors that govern folding and stability of a particular folded protein over the non-organized polypeptide chain. During the past decades a huge amount of thermodynamic data related to protein folding and stability has been accumulated. The data are certainly of importance in dechiffring the protein folding problem. At the same time, the data can guide the con struction of modified and newly synthesized proteins with properties optimized for particular application. The intention of this book is a generation of a data collection which makes the vast amount of present data accessible for multidisciplinary research where chemistry, phy sics, biology, and medicine are involved and also pharmaceutical and food research and technology. It took several years to compile all the data and the author wishes to thank everyone who provided data, ideas or even unpublished results. The author is, in particular, indebted to Prof. Wadso (Lund, Sweden) and IUPAC's Steering Committee on Bio physical Chemistry. Furthermore, support by the Deutsche Forschungsgemeinschafi (INK 16 AI-I) is acknowledged.
