A Physicochemical Analysis of Intrinsically Disordered Peptides Resembling the C-terminal Tail of Saccharomyces Cerevisiae Gamma-tubulin PDF Download

Author: Brandon Payliss
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Book Description
"Microtubules are highly dynamic and essential cytoskeletal structures. They play key roles in cell division and are essential components of the mitotic spindle, which facilitates chromosome separation and segregation into daughter cells. One of the key components in driving the assembly of the mitotic spindle in Saccharomyces cerevisiae is a protein known as [gamma]-tubulin, which has a folded globular domain, followed by an intrinsically disordered carboxyl terminus (CT) rich in glutamate and aspartate residues. Deletion of the last 35 residues of the [gamma]-tubulin CT (or [gamma]-CT) is lethal,1 and mutations in the DSYL motif of the [gamma]-CT can cause spindle defects.2 In this study, we used nuclear magnetic resonance (NMR) spectroscopy and video particle tracking (VPT) microrheology to study the biophysical behaviour of the wildtype [gamma]-CT peptide (WT), but also three mutants where the DSYL motif had been substituted to a DSDL, DDYL, or AAAA, which we have termed the YD, SD, and 4A mutants. One-dimensional NMR diffusion experiments and 1H-15N Heteronuclear Single Quantum Correlation (HSQC) spectroscopy were used to evaluate the impact of increasing acidity on both the diffusion coefficient, as well as the shielding environment of the peptide backbone. Our results show that the WT populates more condensed conformational states with increasing acidity, and that the extent of peak movement for backbone amides in 1H-15N HSQC spectra correlates with the position of ionizable side-chains as pH is reduced. Using VPT microrheology to track 0.2 [mu]m fluorescent beads, we have also studied the viscoelasticity of WT, YD, SD, and 4A peptide solutions. Interestingly, both WT and YD peptide solutions demonstrated subdiffusive properties at pH 7.2 with peptide concentrations 0.1 mM, indicative of liquid-liquid phase separation and/or formation of a system-spanning network. Our results show that subdiffusivity can be ranked WT YD > 4A > SD. Moreover, these results suggest that the [gamma]-CT could play a key role in vivo by promoting liquid-liquid phase separation at the centrosome, and that mutations in the CT could affect these properties." --

Author: Vladimir N. Uversky
Publisher: Springer
ISBN: 3319089218
Category : Science
Languages : en
Pages : 73

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In this brief, Vladimir Uversky discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). Beginning with an introduction to the concept of protein intrinsic disorder, Uversky then goes on to describe the peculiar amino acid sequences of IDPs, their structural heterogeneity, typical functions and disorder-based binding modes. In the final sections, Uversky discusses IDPs in human diseases and as potential drug targets. This volume provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.

Author: Jean-Paul Renaud
Publisher: John Wiley & Sons
ISBN: 1118900502
Category : Medical
Languages : en
Pages : 1367

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Book Description
With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins

Author: A. Ehrenberg
Publisher: Elsevier
ISBN: 148322676X
Category : Science
Languages : en
Pages : 441

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Book Description
Magnetic Resonance in Biological Systems, Volume 9 is a collection of manuscripts presented at the Second International Conference on Magnetic Resonance in Biological Systems, held in Wenner-Gren Center, Stockholm, Sweden on June 1966. The conference is sponsored by International Union of Biochemistry Swedish Medical Research Council Swedish Natural Science Research Council Wenner-Gren Center Foundation for Scientific Research. This book contains 51 chapters, and begins with reviews of NMR investigations of biological macromolecules, including proteins, amino acids, and glycylglycine copper (II). Considerable chapters are devoted to numerous biological studies using the electronic paramagnetic resonance (EPR), thus introducing the branch of science called submolecular biology. This book also explores other applications of NMR and EPR, with special emphasis on blood component analysis and protein-metal complexes. The final chapters survey the principles and applications of Mössbauer spectroscopy. This book will prove useful to analytical chemists and biologists.

Author:
Publisher: Academic Press
ISBN: 0123813506
Category : Science
Languages : en
Pages : 549

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Microtubules: in vivo includes chapters by experts around the world on many aspects of microtubule imaging in living and fixed cells; assays to study microtubule function in a wide array of model organisms and cultured cells; high resolution approaches to study of the cytoskeleton. The authors share their years of experience, outlining potential pitfalls and critical factors to consider in experimental design, experimental implementation and data interpretation. - Includes chapters by experts around the world on many aspects of microtubule imaging in living and fixed cells; assays to study microtubule function in a wide array of model organisms and cultured cells; high resolution approaches to study of the cytoskeleton - The authors share their years of experience, outlining potential pitfalls and critical factors to consider in experimental design, experimental implementation and data interpretation

Author: Dirk Inzé
Publisher: Springer Science & Business Media
ISBN: 9401009368
Category : Science
Languages : en
Pages : 240

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Book Description
In recent years, the study of the plant cell cycle has become of major interest, not only to scientists working on cell division sensu strictu , but also to scientists dealing with plant hormones, development and environmental effects on growth. The book The Plant Cell Cycle is a very timely contribution to this exploding field. Outstanding contributors reviewed, not only knowledge on the most important classes of cell cycle regulators, but also summarized the various processes in which cell cycle control plays a pivotal role. The central role of the cell cycle makes this book an absolute must for plant molecular biologists.

Author: Katrina L. Mealey
Publisher: John Wiley & Sons
ISBN: 1119532574
Category : Medical
Languages : en
Pages : 945

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Book Description
Delivers the foundational and practical knowledge required for pharmacists to become an integral part of the veterinary health care team, improving therapeutic outcome while preventing serious adverse drug reactions in veterinary patients Pharmacotherapeutics for Veterinary Dispensing enables pharmacists and pharmacy students to expand the breadth of their pharmacological knowledge to include common veterinary species. The book offers a practical yet complete resource for dispensing drugs for canine and feline patients, with additional chapters on horses, birds, reptiles, small mammals, and food animals. Edited by a globally recognized expert in veterinary pharmacology, and including chapters written by veterinarians with expertise in pharmacotherapy and pharmacists with expertise in veterinary medicine, this book is designed to help pharmacists enhance the quality of veterinary patient care. This book is the first to combine the expertise of both veterinarians and pharmacists to enable pharmacists to apply their knowledge and skills to assure optimal therapeutic outcomes for patients of all species. Pharmacotherapeutics for Veterinary Dispensing: Puts the information needed to safely dispense prescription and OTC drugs for veterinary patients at the pharmacists’ fingertips Focuses on crucial details of canine and feline pharmacotherapeutics Helps pharmacists avoid adverse drug reactions including pharmacogenomic and breed-related drug sensitivities Offers an authoritative resource written by leading veterinary pharmacy experts designed to integrate pharmacists into the veterinary healthcare team Includes crucial regulatory information unique to veterinary drug dispensing and compounding Pharmacotherapeutics for Veterinary Dispensing is an essential reference for all pharmacists and pharmacy students that might find themselves dispensing drugs to veterinary patients, as well as for veterinarians and others involved with dispensing veterinary drugs. “Pharmacotherapeutics for Veterinary Dispensing is a book long overdue for the pharmacy profession....Whether you have practiced veterinary pharmacy your whole career or have never practiced veterinary pharmacy, this book has much to offer. Veterinarians are encouraged to suggest this book to pharmacists with whom they work and interact.” - JAVMA Vol 255 No. 6

Author: Denis J. Dupré
Publisher: Springer Science & Business Media
ISBN: 9400747659
Category : Medical
Languages : en
Pages : 298

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Main Question: G protein coupled receptors are involved in highly efficient and specific activation of signalling pathways. How do GPCR signalling complexes get assembled to generate such specificity? In order to answer this question, we need to understand how receptors and their signalling partners are synthesized, folded and quality-controlled in order to generate functional proteins. Then, we need to understand how each partner of the signalling complex is selected to join a complex, and what makes this assembly possible. GPCRs are known to be able to function as oligomers, what drives the assembly into oligomers and what will be the effects of such organization on specificity and efficacy of signal transduction. Once the receptor complexes are assembled, they need to reach different locations in the cell; what drives and controls the trafficking of GPCR signalling complexes. Finally, defects in synthesis, maturation or trafficking can alter functionality of GPCRs signalling complexes; how can we manipulate the system to make it function normally again? Pharmacological chaperones may just be part of the answer to this question.

Author: Isabella C. Felli
Publisher: Springer
ISBN: 3319201646
Category : Science
Languages : en
Pages : 428

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Book Description
This book discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). The properties of IDPs and IDPRs are highly complementary to those deriving from the presence of a unique and well-defined three-dimensional fold. Ignored for a long time in high-resolution studies of proteins, intrinsic protein disorder is now recognized as one of the key features for a large variety of cellular functions, where structural flexibility presents a functional advantage in terms of binding plasticity and promiscuity and this volume explores this exciting new research. Recent progress in the field has radically changed our perspective to study IDPs through NMR: increasingly complex IDPs can now be characterized, a wide range of observables can be determined reporting on the structural and dynamic properties, computational methods to describe the structure and dynamics are in continuous development and IDPs can be studied in environments as complex as whole cells. This volume communicates the new exciting possibilities offered by NMR and presents open questions to foster further developments. Intrinsically Disordered Proteins Studied by NMR Spectroscopy provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.

Author: Bhupinder Singh
Publisher: CRC Press
ISBN: 135113888X
Category : Science
Languages : en
Pages : 420

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Book Description
The objective of this book is to provide the fundamental comprehension of a broad range of topics in an integrated volume such that readership hailing from diverse disciplines can rapidly acquire the necessary background for applying it in pertinent research and development field.