Special Issue: Protein Folding

This special issue belongs to the section Biochemistry, Molecular Biology and Biophysics
International Journal of Molecular Sciences (ISSN 1422-0067)

[Editors] [Announced Papers] [Published Papers] [List of Keywords] [Manuscript Submission]

 Manuscript Submisison Deadline: 31 January 2009

 

Editors

Managing Editor
Dr. Shu-Kun Lin
IJMS Editorial Office, MDPI, Kandererstrasse 25, CH-4057, Basel, Switzerland; E-mail: [email protected]
Address manuscript submissions to: Dr. Yuan Gao, E-mail: [email protected]

Editorial Advisor
Prof. Dr. Martin Gruebele
Department of Chemistry, University of Illinois, A220 Chemical & Life Sciences Lab
600 South Mathews Avenue, Urbana, IL 61801, USA
Tel.: +1-(217)333-1624; Fax: +1-(217)244-3186
E-mail: [email protected]
http://www.scs.uiuc.edu/chem/faculty/Martin_Gruebele.html

Keywords (List of topics)
Call for Papers: download the call for paper message here

Manuscript Submission:

You are invited to submit your manuscript by email to [email protected]

Manuscript Submisison Deadline: 31 January 2009

Submitted papers should not have been published previously, nor be currently under consideration for publication elsewhere. All papers are refereed through a peer-review process. A guide for authors and other relevant information for submitting papers are available on the “Instructions for Authors” page.  The International Journal of Molecular Sciences is an international peer-reviewed monthly journal published by Molecular Diversity Preservation International (MDPI).

Announced Papers:
 
Prof. Dr. Martin Gruebele will prepare an overview article that will highlight the contributions to the special issue.
 
Type of Paper: Article
Title: Protein Conformations in Functionalized Nanoporous Polyvinylsiloxane Sol-Gel Glass: Effect of the Crowding Environment and Protein-Silica Interactions.
Authors: Bouzid Menaa 1, #, *, Farid Menaa 2, # Carla Aiolfi-Guimarães 2, Olga Sharts #
Affiliations:1 NanoChem, Department of Chemistry, Nanochemistry and Molecular Systems Laboratory, University of Liege, B6 Sart-Tilman, 4000 Liege, Belgium
2 School of Medicine, University of Würzburg, Josef-Schneider Strasse 2, 97080 Würzburg, Germany
# Fluorotronics, Inc. San Diego Technology Incubator, 1425 Russ Blvd, San Diego, CA 92101, USA
Abstact: We report the conformation of a model protein, apomyoglobin, encapsulated in nanoporous functionalized sol-gel glasses. Polyvinylsiloxane sol-gel glasses have the particularity of bearing an unsaturated organic group susceptible to lead to post-functionalization, so this glass system is very interesting for the study of proteins structure in a crowded environment. The results showed that the encapsulated protein transits from an unfolded state in unmodified glass based on tetramethylmethoxysilane (TMOS) to a native-like helical state in the organically-modified glasses with vinyltrimethoxysilane (VTMS). The helicity of the protein was characterized by circular dichroism and related to to the physical properties of the host matrix to discuss the parameters influencing the protein folding. The results can have a potential impact for the development of new biomaterials (sensors, implanted devises, drug delivery systems) by inducing post-modification of the host matrix and in which properly folded proteins is necessary.
Keywords:Protein folding, polyvinyl-based sol-gel glass, circular dichroism spectroscopy, surface hydration, Atomic Force Microscopy.
 
Type of Paper: Article
Title: Chaperonin Structure - The Large Multi-Subunits Protein Complex
Authors: M. Banach 1,2 and I. Roterman 1,2
Affiliations:1 Department of Bioinformatics and Telemedicine – Jagiellonian University, Collegium Medicum, Lazarza 16, 31-531 Krakow, Poland
2 Faculty of Physics, Astronomy and Applied Computer Science - Jagiellonian University, 30-059 Reymonta 4, Krakow, Poland
Abstact: The proteins are folded in particular environment. According to the model presented in this paper the units participating in complexes are assumed to influence mutually their folding process playing the role of local environment. The large, multi-subunits protein complex - chaperonin - generating specific environment directing the folding process of some proteins are compared with proteins acting as individual molecules and these acting in form of small protein-protein complexes.

Type of Paper: Review
Title: The Discovery of Proteomic Code and mRNA Assisted Protein Folding
Authors: Jan C. Biro
Affiliations: Homulus Foundation, 612 S Flower St , Los Angeles, 90 017 CA, USA
Abstact: The 3x redundancy of the Genetic Code is usually explained as a necessity to increase the mutation-resistance of the genetic information. However the redundant Genetic Code contains biological information which is additional to the 64/20 definition of amino acids. It defines the physico-chemical and structural properties of amino acids, the codon boundaries, the amino acid co-locations (interactions) in the coded proteins and the free folding energy of mRNAs. This additional information is necessary to determine the 3D structure of coding nucleic acids as well as the coded proteins and it is called the Proteomic Code and mRNA Assisted Protein Folding.

Type of Paper: Review
Title: Mechanism of Suppression of Protein Aggregation by α - crystallin
Authors: Kira A. Markossian * and Boris I. Kurganov
Affiliations: Bach Institute of Biochemistry , Russian Academy of Sciences, Leninsky pr. 33, 119071, Moscow , Russia. E-mail: [email protected]
Abstact: The review summarizes experimental data illuminating the mechanism of suppression of protein aggregation by α - crystallin, one of the representatives of small heat shock proteins. The data on dynamic light scattering show that the initial stage of thermal aggregation of proteins is the stage of formation of the start aggregates involving hundreds molecules of denatured protein. Further sticking of the start aggregates proceeds in the regime of diffusion-limited cluster-cluster aggregation. The protective effect of α - crystallin is due to transition of the aggregation process in the regime of reaction-limited cluster-cluster aggregation wherein the sticking probability for colliding particles becomes less than unity.

Type of Paper: Review
Title: Protein Folding and Stabilization by Osmolytes
Authors: Eduardo P. Melo 1 , 2 , Nídia L. Estrela 1, 2, Carlos Lopes 1, Vanessa Ochoa-Mendes 2 and Joaquim M. S. Cabral 2
Affiliations:1 Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine, Univ. of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal
2 Institute for Biotechnology and Bioengineering, Centro de Engenharia Biológica e Química, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
Abstact: Osmolytes accumulate intracellularly as a response to stress conditions and are widely used to increase the stability and lifetime of proteins. In this review we will characterize the mechanism and thermodynamics of protein stabilization by osmolytes using mostly trehalose as the model compound. The mechanism of protein stabilization was assessed by stability measurements but also through the analysis of protein folding/unfolding pathways measured by kinetics. Osmolytes stabilize proteins by shifting the equilibrium towards the folded state, thus delaying both thermal and chemical-induced protein unfolding [1, 2]. Interestingly, the effect of osmolytes on the prevention of irreversible pathways, such as aggregation, is assigned only to their effect on reversible unfolding. Characterization of protein unfolding pathways, namely the presence of intermediates between folded and unfolded states, reveal that osmolytes do not change the nature of the unfolding pathway [3, 4, 5]. They only shift the equilibrium towards more compact species. On contrary, osmolytes do change the folding pathway by favoring compact intermediates that accumulate off-pathway [4, 6]. The accumulation of compact off-folding states might be a "side-effect" of the mechanism of protein stabilization by osmolytes which promote protein compaction [7] decreasing the conformational space accessible to the unfolded state. The unfolded state acquires residual native interactions in the presence of osmolytes that channel the folding of the protein supporting recent recognition that residual structure in the unfolded state might be an important mechanism for tuning protein stability [5, 6].
References: 1. Baptista, R.P.; Cabral, J.M.S.; Melo, E.P. Biotechnol. Bioeng. 2000, 70, 699-703; 2. Baptista, R.P.; Chen, L.Y.; Paixão, A.; Cabral, J.M.S.; Melo, E.P. Biotechnol. Bioeng. 2003, 82, 851-857; 3. Melo, E.P.; Faria,T.Q.; Martins, L.O.; Gonçalves, A.M.; Cabral, J.M.S. Proteins 2001, 42, 542-552; 4. Melo, E.P.; Chen, L.Y.; Cabral, J.M.S.; Fojan, P.; Petersen, S.B.; Otzen, D.E. Biochemistry-US 2003, 42, 7611-7617; 5. Baptista, R.P.; Pedersen, S.; Cabrita, G.J.M.; Otzen, D.E.; Cabral, J.M.S.; Melo, E.P. Biopolymers 2008, 89, 538-547; 6. Chen, L.Y.; Cabrita, G.J.M.; Otzen, D.E.; Melo, E.P. J. Mol. Biol. 2005, 351, 402-416; 7. Chen, L.Y.; Ferreira, J.A.B.; Costa, S.M.B.; Cabrita, G.J.M.; Otzen, D.E.; Melo, E.P. Biochemistry-US 2006, 45, 2189-2199.

Type of Paper: Article
Title: Probing the Structure of the Immunologically Active Truncated Human Thioredoxin
Authors: María Luisa Tasayco, Glorymar Ibañez, Franya Sanchez, Luis Ramírez, Cristian Valencia, and Gary López
Affiliations: Department of Chemistry, City College of New York, 138th Street and Convent Avenue, New York, NY 10031, USA
Abstact: Secreted 12KDa full length human thioredoxin (Hu trx) has a chemoattractant activity associated with its redox active disulfide bond. In contrast, a secreted truncated human thioredoxin (Trx80) encompassing the first 80 amino acids shows a disulfide-independent mitogenic and eosinophilic cytotoxic-enhancing activity and ability to bind to the outer membrane of monocytes (Holmgren et al). The structural basis for the difference in biological activity of Hu trx and Trx80 is still unknown, even though our previous studies on E. coli trx suggests that Trx80 preserves the nativelike packing of the central ß-strands. We have conducted a biophysical study of Trx80 and a set of mutants in solution. The dynamic light scattering analysis reveals aggregating tendencies in Trx80 and its Far-UV circular dichroism analysis indicates the presence of both secondary structure and statistical random coil. To probe the expected nativelike regions in Trx80, fluorescence energy transfer analysis was conducted on mutants of both Trx80 and Hu trx. To gather insight about the random coil regions in Trx80, a 3D-NMR analysis at increasing denaturant concentrations was carried out and compared against that of fragments (1—37, 1—82, 38—105, 75—105) derived from Hu trx. Our results lead us to suggest a model of Trx80 with nativelike features.

Type of Paper: Review
Title: Folding, Structure and Stability of Proteins in Crowded Environments: Experimental and Computational Approaches
Authors: Margaret S. Cheung 1 and Pernilla Wittung-Stafshede 2
Affiliations: 1 Department of Physics, University of Houston, Houston, Texas 77204, USA
2 Department of Chemistry, Umea University, Umea, 90187 Sweden
Abstact: How the crowded environment inside cells affects folding, stability and structures of proteins is a vital question since most proteins are made and function inside cells. Here we describe how crowded conditions can be created in vitro and in silico to probe effects on protein properties. We have found that unrelated proteins become more ordered and compact in the presence of macromolecular crowding agents; if the protein is non-spherical, the shape also changes (extent dictated by stability and chemical conditions). As expected, the native states of the proteins are stabilized relative to the unfolded states in crowded conditions. It was also discovered that the shape of the macromolecular crowding agent modulates the folding mechanism of the protein.
Keywords: Macromolecular crowding, Ficoll 70, energy landscape theory, off-lattice model, excluded volume effect, protein folding mechanism, spectroscopy.

Type of Paper: Review
Title: Slow Unfolding of Hyperthermophilic Proteins
Authors: Atsushi Mukaiyama 1 and Kazufumi Takano 2, 3,*
Affiliations: 1 Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan
2 Department of Material and Life Science, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: [email protected]
3 CREST, JST, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Abstact: Microorganisms can be classified into psychrophiles, mesophiles, thermophiles, or hyperthermophiles based on the differences in their optimal growth temperatures. Proteins from hyperthermophiles generally reveal greater stability than those from any other microorganisms. Therefore, proteins from hyperthermophiles are expected to provide unique or general insight into protein folding and stability. In this review, we describe recent studies about the stability and folding of hyperthermophilic proteins with respect to the equilibrium and kinetic aspects. The stabilization mechanism of hyperthermophilic proteins is found to be characterized by slow unfolding and this appears to be a common characteristic of hyperthermophilic proteins. Furthermore, various stabilizing factors such as ion pairs and hydrophobic interactions are known to be involved in the stabilization of proteins. We discuss the contribution of these factors on the stability and folding of hyperthermophilic proteins.

Type of Paper: Review
Title: Protein Folding and Misfolding on Surfaces
Authors: Massimo Stefani
Affiliations: Dept. of Biochemical Sciences, Research Centre on the Molecular Basis of Neurodegeneration, University of Florence, V.le Morgagni 50, 50134 Florence, Italy
Abstact: Protein folding is a key topic in cell biology, being paradigmatic of biological self-assembly; it is also the basis to understand protein misfolding and aggregation, two processes underlying many human diseases. Folded/misfolded proteins and peptides as well as toxic amyloid aggregates are able to interact with cell membranes impairing their structural organization and destroying their selective ion permeability with early alterations of the intracellular redox status and ion homeostasis eventually culminating with cell death. Each of these steps is most likely influenced by the physicochemical features and the aggregation state of amyloids as well as by the physical and biochemical features of the membranes themselves in ways that are still under investigation. More generally, the role of synthetic and biological surfaces in speeding up the rate of aggregate nucleation and as key targets of toxic aggregates is gaining rising consideration. Recent research has highlighted the roles performed by surfaces as enhancers of either protein folding or as protein misfolding chaperones and aggregation catalysts and by their physical and biochemical features in affecting all these phenomena.

Type of Paper: Review
Title: Polymorphyism of Parallel and Antiparallel Alzheimer Aβ Oligomer Organization
Authors: Yifat Miller 1 Buyong Ma 2 and Ruth Nussinov 2, 3
Affiliations: 1 Center for Cancer Research Nanobiology Program NCI-Frederick, Frederick, MD 21702
2 Basic Research Program, SAIC-Frederick, Inc. Center for Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD 21702
3 Sackler Inst. of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Abstact: Aβ peptide and its fragments aggregate mostly with parallel β-sheet organization. Recent experiments suggest that the antiparallel β-sheet organization could also contribute to the amyloid fiber. Our results suggest a competition between the parallel and antiparrallel β-sheet organization. Here, we have used molecular dynamics simulations to investigate the stabilities of parallel and anti-parallel Aβ1-42 and Aβ17-42 oligomer organizations. While the parallel Aβ1-42 is more stable than antiparallel, a stable antiparallel Aβ17-42 organization does exist. Interestingly, antiparallel conformations have a more pronounced tendency to form ion channels than parallel by forming larger cavity within the double layer of U-shaped Aβ peptides.

Type of Paper: Review
Title: Protection of Neurons from Conformational Disease by Molecular Chaperones
Authors: Peter M. Douglas, Daniel W. Summers, Douglas M. Cyr
Affiliations: Department of Cell and Developmental Biology, School of Medicine , University of North Carolina, Chapel Hill , NC 27599-7090
Abstact: The self-association of misfolded or damaged proteins into ordered amyloid-like aggregates underlies numerous neurodegenerative disorders. Insoluble amyloid plaques are diagnostic of many disease states yet soluble intermediates in the aggregation pathway may represent the toxic culprit. Molecular chaperones regulate the fate of these misfolded proteins and thereby influence their aggregation state. Chaperones conventionally reduce intracellular protein aggregation by directly binding to the misfolded substrate or disassembling pre-existing aggregates. Recent work suggests that chaperones may also suppress neurotoxicity by converting soluble, toxic species into benign aggregates. Chaperones can therefore either suppress or promote protein aggregation to ameliorate the accumulation of neurotoxic protein species.

Type of Paper: Review
Title: Protein Folding-unfolding at High Pressure
Authors: László Smeller
Affiliations: Dept Biophysics and Radiation Biology, Semmelweis University , Budapest
Abstact: Although biological processes and protein folding among them occur at atmospheric pressure, studies of protein folding at high pressure can extend our knowledge, in a similar way like the experiments as function of temperature or denaturant concentration do. Pressure can distort the folded structure and high enough pressures (typically around 500 MPa) can even unfold the protein. This makes pressure jump experiments a useful tool to study the kinetics of folding. After brief summary of the pressure-temperature phase diagram of the proteins, from the point of view of existence of different stable and metastable conformations, pressure jump experiments will be reviewed. Kinetics of competing folding and misfolding processes after negative pressure jump from unfolding pressures to ambient one will be analyzed.

Type of Paper: Review
Title: Participation of Low Molecular Weight Electron Carriers in the Oxidative Protein Folding
Authors: Éva Margittai, Miklós Csala, József Mandl and Gábor Bánhegyi
Affiliations: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University & MTA-SE Pathobiochemistry Research Group, Budapest , Hungary
Abstact: Oxidative protein folding is mediated by a proteinaceous electron relay system, in which the concerted action of protein disulfide isomerase and Ero1p delivers the electrons from thiol groups to the final acceptor. Oxygen appears to be the final oxidant in aerobic living organisms, although the existence of alternative electron acceptors, e.g. fumarate or nitrate, cannot be excluded. Whilst the protein components of the system are well-known, less attention has been turned to the role of low molecular weight electron carriers in the process. The function of ascorbate, tocopherol and vitamin K has been raised recently. In vitro and in vivo evidence suggests that these redox-active compounds can contribute to the functioning of oxidative folding. This review focuses on the participation of small molecular weight redox compounds in oxidative protein folding.

Type of Paper: Review
Title: Effect of Nanoparticles on Protein Folding and Fibrillogenesis
Authors: Li Fei and Sarah Perrett*
Affiliations: National Laboratory of Biomacromoleules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101
Abstract: Nanoparticles are between 1-100 nm in size and vary in shape, composition and surface properties. Their large surface area and small size provide properties and applications that are distinct from those of bulk materials. The ability of nanoparticles to influence protein folding and aggregation is interesting not only because of the potential application of nanoparticles as pharmaceuticals, sensors or switches, but also because of concerns about the risks of nanomaterials to human health and the environment. This makes it essential that we understand the effect of nanoparticles on fundamental biological process, such as protein folding and function. Formation of fibrillar protein aggregates is associated with a number of human diseases, including Alzheimer’s, Parkinson’s, diabetes and prion diseases, due to misfolding of specific amyloidogenic proteins or peptides. Fibrillar peptide-based nanomaterials have also been produced, and functionalisation of these nanomaterials has a wide range of potential applications in medicine and biotechnology. Here, we review studies that have examined the effect of nanoparticles on the folding and aggregation of proteins, providing insight both into the mechanisms of these processes and how they may be controlled. We also review the design and application of polypeptide-based fibrillar nanomaterials. The potential benefits and risks are discussed.

Type of Paper: Review
Title: Folding by Numbers: The Use of Statistics for Understanding Protein Folding
Authors: Zongchao Jia
Affiliation: Department of Biochemistry Queen's University Kingston, Ontario K7L 3N6 Canada
Abstract: The exponential growth over the past several decades in both the quantity of primary sequence data available and the number of protein structures determined has provided a wealth of information describing the relationship between protein sequence and structure.  This growing repository has served as a prime source for statistical analysis, where underlying relationships between patterns of amino acids and tertiary protein structure can be uncovered.  Here, we review the main statistical techniques that have been used for studying protein folding, and describe the major contributions to the field that have arisen from these techniques, including secondary structure prediction, helical stability theories involving helix capping, and statistical potentials, among others.  We also describe two novel statistical studies of secondary structure, the main conclusions of both being that the major secondary structural elements are predominantly nucleated at their termini, with subsequent unidirectional growth.  Limitations to statistical analyses are discussed, and a context for their role within the field of protein folding is given.

Type of paper: Review
Title: Protein Folding and Misfolding Probed by FTIR Techniques
Authors: Heinz Fabian and Dieter Naumann
Affiliation: Robert Koch-Institute, P25, Berlin, Germany
Abstract: Recently progress has been achieved in the adaptation of conventional mixing or temperature-jump technologies to the specific requirements of Fourier transform infrared (FTIR) spectroscopy. Here we describe experimental methodologies that are capable of initiating and monitoring protein folding and misfolding events in the millisecond to minute timescale. The FT-IR approach is instrumental in monitoring simultaneously changes in secondary structure of proteins and in the microenvironment of certain amino acid side-chain groups. To illustrate this point, we discuss temperature-induced folding events of the proteins ribonuclease T1 and λ-Cro repressor. Moreover, misfolding events of the prion protein and of β2-microglobulin probed by stopped-flow FTIR are described.
 
Published Papers:
 
Open Access
Callise M. Ollom and John B. Denny *
Department of Ophthalmology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA. E-Mail: [email protected] (C. O.)
* Author to whom correspondence should be addressed; E-Mail: [email protected]
Received: 13 August 2008; in revised form: 3 September 2008 / Accepted: 13 September 2008 / Published: 16 September 2008
Article: A Crosslinking Analysis of GAP-43 Interactions with Other Proteins in Differentiated N1E-115 Cells
Int. J. Mol. Sci. 2008, 9, 1753-1771 (PDF format, 1102K); DOI: 10.3390/ijms9091753

 
International Journal of Molecular Sciences (ISSN 1422-0067)
Last change: 16 September 2008
© 2008 by MDPI, Basel, Switzerland