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Author: Bruce Alberts
Publisher:
ISBN: 9780815332183
Category : Cytology
Languages : en
Pages : 0
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Author: Bruce Alberts
Publisher:
ISBN: 9780815332183
Category : Cytology
Languages : en
Pages : 0
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Author: Robert Pilstål
Publisher: Linköping University Electronic Press
ISBN: 9176853470
Category :
Languages : en
Pages : 206
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Book Description
We are compounded entities, given life by a complex molecular machinery. When studying these molecules we have to make sense of a diverse set of dynamical nanostructures with wast and intricate patterns of interactions. Protein polymers is one of the major groups of building blocks of such nanostructures which fold up into more or less distinct three dimensional structures. Due to their shape, dynamics and chemical properties proteins are able to perform a plethora of specific functions essential to all known cellular lifeforms. The connection between protein sequence, translated into protein structure and in the continuation into protein function is well accepted but poorly understood. Malfunction in the process of protein folding is known to be implicated in natural aging, cancer and degenerative diseases such as Alzheimer's. Protein folds are described hierarchically by structural ontologies such as SCOP, CATH and Pfam all which has yet to succeed in deciphering the natural language of protein function. These paradigmatic views centered on protein structure fail to describe more mutable entities, such as intrinsically disordered proteins (IDPs) which lack a clear defined structure. As of 2012, about two thirds of cancer patients was predicted to survive past 5 years of diagnosis. Despite this, about a third do not survive and numerous of successfully treated patients suffer from secondary conditions due to chemotherapy, surgery and the like. In order to handle cancer more efficiently we have to better understand the underlying molecular mechanisms. Elusive to standard methods of investigation, IDPs have a central role in pathology; dysfunction in IDPs are key factors in cellular system failures such as cancer, as many IDPs are hub regulators for major cell functions. These IDPs carry short conserved functional boxes, that are not described by known ontologies, which suggests the existence of a smaller entity. In an investigation of a pair of such boxes of c-MYC, a plausible structural model of its interacting with Pin1 emerged, but such a model still leaves the observer with a puzzle of understanding the actual function of that interaction. If the protein is represented as a graph and modeled as the interaction patterns instead of as a structural entity, another picture emerges. As a graph, there is a parable from that of the boxes of IDPs, to that of sectors of allosterically connected residues and the theory of foldons and folding units. Such a description is also useful in deciphering the implications of specific mutations. In order to render a functional description feasible for both structured and disordered proteins, there is a need of a model separate from form and structure. Realized as protein primes, patterns of interaction, which has a specific function that can be defined as prime interactions and context. With function defined as interactions, it might be possible that the discussion of proteins and their mechanisms is thereby simplified to the point rendering protein structural determination merely supplementary to understanding protein function. Människan byggs upp av celler, de i sin tur består av än mindre beståndsdelar; livets molekyler. Dessa fungerar som mekaniska byggstenar, likt maskiner och robotar som sliter vid fabrikens band; envar utförandes en absolut nödvändig funktion för cellens, och hela kroppens, fortsatta överlevnad. De av livets molekyler som beskrivs centralt i den här avhandling är proteiner, vilka i sin tur består utav en lång kedja, med olika typer av länkar, som likt garn lindar upp sig i ett nystan av en (mer eller mindre...) bestämd struktur som avgör dess roll och funktion i cellen. Intrinsiellt oordnade proteiner (IDP) går emot denna enkla åskådning; de är proteiner som saknar struktur och beter sig mer likt spaghetti i vatten än en maskin. IDP är ändå funktionella och bär på centrala roller i cellens maskineri; exempel är oncoproteinet c-Myc som agerar "gaspedal" för cellen - fel i c-Myc's funktion leder till att cellerna löper amok, delar sig hejdlöst och vi får cancer. Man har upptäckt att c-Myc har en ombytlig struktur vi inte kan se; studier av punktvisa förändringar, mutationer, i kedjan av byggstenar hos c-Myc visar att många länkar har viktiga roller i funktionen. Detta ger oss bättre förståelse om cancer men samtidigt är laboratoriearbetet både komplicerat och dyrt; här kan evolutionen vägleda oss och avslöja hemligheterna snabbare. Molekylär evolution studeras genom att beräkna variation i proteinkedjan mellan besläktade arter som finns lagrade i databaser; detta visar snabbt, via nätverksanalys och grafteori, vilka delar av proteinet som är centrala och kopplade till varandra av nödvändighet för artens fortlevnad. På så vis hjälper evolutionen oss att förstå proteinfunktioner via modeller baserade på proteinernas interaktioner snarare än deras struktur. Samma modeller kan nyttjas för att förstå dynamiska förlopp och skillnader mellan normala och patologiska varianter av proteiner; mutationer kan uppstå i vår arvsmassa som kan leda till sjukdom. Genom analys av proteinernas kopplingsnätverk i grafmodellerna kan man bättre förutsäga vilka mutationer som är farligare än andra. Dessutom har det visat sig att en sådan representation kan ge bättre förståelse för den normala funktionen hos ett protein än vad en proteinstruktur kan. Här introduceras även konceptet proteinprimärer, vilket är en abstrakt representation av proteiner centrerad på deras interaktiva mönster, snarare än på partikulär form och struktur. Det är en förhoppning att en sådan representation skall förenkla diskussionen anbelangande proteinfunktion så till den grad att strukturbestämmelse av proteiner, som är en mycket kostsam och tidskrävande process, till viss mån kan anses vara sekundär i betydelse jämfört med funktionellt modellerande baserat på evolutionära data extraherade ur våra sekvensdatabaser.
Author: Inga-Maria Frick
Publisher:
ISBN:
Category : Bacterial immunoglobin-binding proteins
Languages : en
Pages : 154
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Book Description
Author: Vernon Bryson
Publisher: Academic Press
ISBN: 1483266303
Category : Science
Languages : en
Pages : 654
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Book Description
Evolving Genes and Proteins covers the proceedings of the "Evolving Genes and Proteins" symposium, held at the Institute of Microbiology of Rutgers, The State University on September 17 and 18, 1964, with support from the National Science Foundation. The book focuses on the structural and functional features of proteins and nucleic acids. The selection first offers information on lysine biosynthesis and evolution, lipid patterns in the evolution of organisms, and evolution of heme and chlorophyll. Discussions focus on the evolution of the genes of the porphyrin biosynthetic chain, polyunsaturated fatty acids in plants and animals, and diagnostic radiocarbon tracers. The text then examines evolutionary divergence and convergence in proteins; evolution of hemoglobin in primates; and constancy and variability of protein structure in respiratory and viral proteins. The publication takes a look at the comparative aspects of the structure and function of phosphoglucomutase, evolution of dehydrogenases, and enzymatic homology and analogy in phylogeny. The text also ponders on the evolution of an enzyme, role of mutations in evolution, enzyme catalysis and color of light in bioluminescent reactions, and evolution of the lactose utilization gene system in enteric bacteria. The selection is a valuable reference for microbiologists and readers interested in the study of genes and proteins.
Author: Anna Wehlin
Publisher:
ISBN: 9789180752589
Category :
Languages : en
Pages : 0
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Author: Eugene V. Koonin
Publisher: Springer Science & Business Media
ISBN: 1475737831
Category : Science
Languages : en
Pages : 482
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Book Description
Sequence - Evolution - Function is an introduction to the computational approaches that play a critical role in the emerging new branch of biology known as functional genomics. The book provides the reader with an understanding of the principles and approaches of functional genomics and of the potential and limitations of computational and experimental approaches to genome analysis. Sequence - Evolution - Function should help bridge the "digital divide" between biologists and computer scientists, allowing biologists to better grasp the peculiarities of the emerging field of Genome Biology and to learn how to benefit from the enormous amount of sequence data available in the public databases. The book is non-technical with respect to the computer methods for genome analysis and discusses these methods from the user's viewpoint, without addressing mathematical and algorithmic details. Prior practical familiarity with the basic methods for sequence analysis is a major advantage, but a reader without such experience will be able to use the book as an introduction to these methods. This book is perfect for introductory level courses in computational methods for comparative and functional genomics.
Author: David S. Sigman
Publisher: Elsevier
ISBN: 1483262812
Category : Science
Languages : en
Pages : 369
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Book Description
The Evolution of Protein Structure and Function documents the proceedings of the symposium ""Evolution of Protein Structure and Function"" held at the Dickson Art Auditorium, University of California Los Angeles (UCLA), 28-29 June 1979. Its objective was to honor Professor Emil L. Smith on the occasion of his retirement as Professor and Chairman, Department of Biological Chemistry, School of Medicine, UCLA. The papers presented by Emil’s colleagues, friends, and students from all phases of his long and varied scientific career provided a valuable review of enzymology, protein chemistry, and biochemical evolution. The volume contains 16 chapters is organized into three parts. Part I contains papers on enyzmology, including the role of the recA protein of Escherichia coli in general recombination; the evolution of enzyme families; and studies on metalloenzymes. Part II takes up protein structure and function. It includes papers on glycoprotein hormones, thymus hormones, chromosome biology and chemistry, and the evolution of histones. Part III examines the evolution of proteins, including the evolution of cythochrome c and evolution of phycobilisome of cyanobacteria and red algae.
Author: Laszlo Patthy
Publisher: John Wiley & Sons
ISBN: 1444308882
Category : Science
Languages : en
Pages : 392
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Book Description
This book provides an up-to-date summary of the principles of protein evolution and discusses both the methods available to analyze the evolutionary history of proteins as well as those for predicting their structure-function relationships. Includes a significantly expanded chapter on genome evolution to cover genomes of model organisms sequenced since the completion of the first edition, and organelle genome evolution Retains its reader-friendly, accessible style and organization Contains an updated glossary and new references, including a list of online reference sites
Author: Jay F. Storz
Publisher: Oxford University Press
ISBN: 0192538764
Category : Science
Languages : en
Pages : 272
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Book Description
The primary aim of this book is to provide a synthesis of our current understanding of hemoglobin function and evolution, and to illustrate how research on one particular family of proteins has provided general insights into mechanisms of protein evolution and biochemical adaptation. In doing so, it will also promote an appreciation of how mechanistic insights into protein function can enrich our understanding of how evolution works. Reciprocally, it highlights how approaches in evolutionary genetics (such as phylogenetic comparative methods and ancestral sequence reconstruction) can be brought to bear on questions about the functional evolution of proteins. This treatise on the functional evolution of hemoglobin illustrates how research on a single, well-chosen model system can enhance our investigative acuity and bring key conceptual questions into especially sharp focus.
Author:
Publisher: Elsevier
ISBN: 0080493378
Category : Science
Languages : en
Pages : 451
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Book Description
This is the first high-quality, comprehensive overview of the field of evolutionary protein design. Topics include new protein design strategies, the structures of laboratory-evolved proteins, the evolution of non-natural enzyme functions, and the theory of laboratory evolution.
