Moonlighting Proteins

Moonlighting Proteins: Novel Virulence Factors in Bacterial Infections is a complete examination of the ways in which proteins with more than one unique biological action are able to serve as virulence factors in different bacteria. The book explores the pathogenicity of bacterial moonlighting proteins, demonstrating the plasticity of protein evolution as it relates to protein function and to bacterial communication. Highlighting the latest discoveries in the field, it details the approximately 70 known bacterial proteins with a moonlighting function related to a virulence phenomenon. Chapters describe the ways in which each moonlighting protein can function as such for a variety of bacterial pathogens and how individual bacteria can use more than one moonlighting protein as a virulence factor. The cutting-edge research contained here offers important insights into many topics, from bacterial colonization, virulence, and antibiotic resistance, to protein structure and the therapeutic potential of moonlighting proteins. Moonlighting Proteins: Novel Virulence Factors in Bacterial Infections will be of interest to researchers and graduate students in microbiology (specifically bacteriology), immunology, cell and molecular biology, biochemistry, pathology, and protein science.

Autorentext

Brian Henderson is Professor of Biochemistry in the Department of Microbial Diseases at the UCL-Eastman Dental Institute, University College London. He has worked in academia, both in the UK and North America, and also in the pharmaceutical and biopharmaceutical industry. He has been a cell biologist, immunologist and pharmacologist and over the past twenty years has focused on bacteria-host interactions in relation to human infection and the maintenance of the human microbiota. This is the discipline of Cellular Microbiology and Henderson published the first book on this subject in 1999. At the inception of his career as a cellular microbiologist he discovered a potent bone-destroying protein generated by a pathogenic bacterium. This protein, surprisingly, was the cell stress protein, heat shock protein (Hsp)60. This was one of the earliest bacterial moonlighting proteins discovered and is the reason that the editor has spent the last 20 years exploring the role of protein moonlighting in the life of the bacterium and its interactions with its human host. Henderson has written or edited 17 books and monographs and was the senior editor of the Cambridge University Press Monograph series: Advances in Molecular and Cellular Microbiology.

Klappentext
Moonlighting Proteins: Novel Virulence Factors in Bacterial Infections is a complete examination of the ways in which proteins with more than one unique biological action are able to serve as virulence factors in different bacteria.

The book explores the pathogenicity of bacterial moonlighting proteins, demonstrating the plasticity of protein evolution as it relates to protein function and to bacterial communication. Highlighting the latest discoveries in the field, it details the approximately 70 known bacterial proteins with a moonlighting function related to a virulence phenomenon. Chapters describe the ways in which each moonlighting protein can function as such for a variety of bacterial pathogens and how individual bacteria can use more than one moonlighting protein as a virulence factor. The cutting-edge research contained here offers important insights into many topics, from bacterial colonization, virulence, and antibiotic resistance, to protein structure and the therapeutic potential of moonlighting proteins.

Moonlighting Proteins: Novel Virulence Factors in Bacterial Infections will be of interest to researchers and graduate students in microbiology (specifically bacteriology), immunology, cell and molecular biology, biochemistry, pathology, and protein science.

About the Editor
Brian Henderson, Division of Infection and Immunity, University College London, London, UK

Inhalt

List of Contributors xv

Preface xix

About the Editor xxiii

Part I Overview of Protein Moonlighting 1

1 What is Protein Moonlighting and Why is it Important? 3
Constance J. Jeffery

1.1 What is Protein Moonlighting? 3

1.2 Why is Moonlighting Important? 5

1.2.1 Many More Proteins Might Moonlight 5

1.2.2 Protein Structure/Evolution 5

1.2.3 Roles in Health and Disease 8

1.2.3.1 Humans 8

1.2.3.2 Bacteria 10

1.3 Current questions 11

1.3.1 How Many More Proteins Moonlight? 11

1.3.2 How Can We Identify Additional Proteins That Moonlight and all the Moonlighting Functions of Proteins? 11

1.3.3 In Developing Novel Therapeutics, How Can We Target the Appropriate Function of a Moonlighting Protein and Not Affect Other Functions of the Protein? 12

1.3.4 How do Moonlighting Proteins get Targeted to More Than One Location in the Cell? 12

1.3.5 What Changes in Expression Patterns Have Occurred to Enable the Protein to be Available in a New Time and Place to Perform a New Function? 12

1.4 Conclusions 13

References 13

2 Exploring StructureFunction Relationships in Moonlighting Proteins 21
Sayoni Das, Ishita Khan, Daisuke Kihara, and Christine Orengo

2.1 Introduction 21

2.2 Multiple Facets of Protein Function 22

2.3 The Protein StructureFunction Paradigm 23

2.4 Computational Approaches for Identifying Moonlighting Proteins 25

2.5 Classification of Moonlighting Proteins 26

2.5.1 Proteins with Distinct Sites for Different Functions in the Same Domain 27

2.5.1.1 Enolase, Streptococcus pneumonia 27

2.5.1.2 Albaflavenone monooxygenase, Streptomyces coelicolor A*3(2)* 29

2.5.1.3 MAPK1/ERK2, Homo sapiens 30

2.5.2 Proteins with Distinct Sites for Different Functions in More Than One Domain 30

2.5.2.1 Malate synthase, Mycobacterium tuberculosis 31

2.5.2.2 BirA, Escherichia coli 31

2.5.2.3 MRDI, Homo sapiens 33

2.5.3 Proteins Using the Same Residues for Different Functions 33

2.5.3.1 GAPDH E. coli 33

2.5.3.2 Leukotriene A4 hydrolase, Homo sapiens 33

2.5.4 Proteins Using Different Residues in the Same/Overlapping Site for Different Functions 34

2.5.4.1 Phosphoglucose isomerase, Oryctolagus cuniculus, Mus musculus, Homo sapiens 34

2.5.4.2 Aldolase, Plasmodium falciparum 36

2.5.5 Proteins with Different Structural Conformations for Different Functions 36

2.5.5.1 RfaH, E. coli 36

2.6 Conclusions 37

References 39

Part II Proteins Moonlighting in Prokarya 45

3 Overview of Protein Moonlighting in Bacterial Virulence 47
Brian Henderson

3.1 Introduction 47

3.2 The Meaning of Bacterial Virulence and Virulence Factors 47

3.3 Affinity as a Measure of the Biological Importance of Proteins 49

3.4 Moonlighting Bacterial Virulence Proteins 50

3.4.1 Bacterial Proteins Moonlighting as Adhesins 52

3.4.2 Bacterial Moonlighting Proteins That Act as Invasins 59

3.4.3 Bacterial Moonlighting Proteins Involved in Nutrient Acquisition 59

3.4.4 Bacterial Moonlighting Proteins Functioning as Evasins 60

3.4.5 Bacterial Moonlighting Proteins with Toxinlike Actions 63

3.5 Bacterial Moonlighting Proteins Conclusively Shown to be Virulence Factors 64

3.6 Eukaryotic Moonlighting Proteins That Aid in Bacterial Virulence 66

3.7 Conclusions 67

References 68 4 Moonlighting Proteins as CrossReactive AutoAntigens 81
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