Download Free Collagen Binding I Domain Integrins What Do They Do Book in PDF and EPUB Free Download. You can read online Collagen Binding I Domain Integrins What Do They Do and write the review.

The integrin family is composed of 24 members and approximately ten years ago (2003) we published a book devoted to the nine I domain integrin subunits. In this second edition, I am pleased that most of the original authors have been able to contribute to the updated version. I domain containing integrins include collagen receptors and leukocyte receptors. In 2003 the knockout mouse phenotypes for all of the I domain integrins had not yet been published; they are now, and are summarized and discussed in this edition. Interestingly, a recent 10 integrin mutation in dogs has indicated that collagen-binding integrins in the musculoskeletal system might have much more severe phenotypes in larger animals/humans compared to the mild integrin phenotypes observed in collagen-binding integrin deficient mice. This finding is further discussed in the book. In the cancer field, the microenvironment is taking center stage, and here collagen receptors on fibroblasts are predicted to play important roles in paracrine signaling, in regulating tissue stiffness and matrix remodeling. New technologies, new mouse models in combination with analyses of I integrins in larger animals/humans are thus predicted to increase our knowledge about this group of receptors. With this in mind we look forward to another 10 years of research with I domain integrins.
Integrins comprise of a large family of heterodimeric cell adhesion receptors consisting of an [alpha]- and a [beta]- subunit. They are responsible for mediating cell-cell and cell-extracellular matrix (ECM) interactions. In addition, they transmit bi-directional (outside-in and inside- out) signals across the plasma membrane, regulating numerous important cellular behaviours including cell adhesion, cell migration and cell communication. Collagen-binding integrins represent one of the five integrin subfamilies and are characterized by their ligand specificity for different collagens. Each [alpha] subunit in the collagen-binding subfamily contains an inserted domain, the [alpha]I domain, which is responsible for collagen binding. The interactions between two of the most studied collagen-binding integrins, [alpha]1[beta]1 and [alpha]2[beta]1, and their respective collagen substrates have been implicated in several disease processes, making these receptors attractive therapeutic targets.The initial aim of this project was to identify small molecule scaffolds that are suitable starting points for designing inhibitors of the [alpha]1[beta]1-collagen interaction. The approach adopted was fragment-based drug discovery. The lack of structural information on the collagen-bound state of [alpha]1I domain, however, made the process very challenging. Therefore, it was decided that the structure of the [alpha]1I domain-collagen complex should be characterised to support any subsequent program of rational drug design from the fragment-based approach.A variety of techniques were employed to characterise the interactions between [alpha]1I domain and synthetic collagen peptides. These included surface plasmon resonance spectroscopy (SPR) which provided details of the affinity and kinetics of binding, size exclusion chromatography and small angle X-ray scattering that revealed an unexpected stoichiometry of binding, NMR experiments that enabled the structure of [alpha]1I domain to be determined in the presence of a collagen peptide and computer docking using the data-driven docking program, HADDOCK, to generate a model of the entire [alpha]1I domain-collagen peptide complex. Combining the information generated from all these techniques in conjunction with previously reported structural and mutagenesis studies, a detailed insight into the interaction was provided. Not only do these results provide a structural rationale to design inhibitors of collagen binding to [alpha]1I domain, they are also valuable for understanding the biological roles and the regulation of this receptor.
An integrin, or integrin receptor, is an integral membrane protein in the plasma membrane of cells. It plays a role in the attachment of a cell to the extracellular matrix (ECM) and to other cells, and in signal transduction from the ECM to the cell. There are many types of integrin, and many cells have multiple types on their surface. Integrins are of vital importance to all metazoans, from humans to sponges. This volume in Methods in Enzymology presents methods for studying integrins.
Lung Epithelial Biology in the Pathogenesis of Pulmonary Disease provides a one-stop resource capturing developments in lung epithelial biology related to basic physiology, pathophysiology, and links to human disease. The book provides access to knowledge of molecular and cellular aspects of lung homeostasis and repair, including the molecular basis of lung epithelial intercellular communication and lung epithelial channels and transporters. Also included is coverage of lung epithelial biology as it relates to fluid balance, basic ion/fluid molecular processes, and human disease. Useful to physician and clinical scientists, the contents of this book compile the important and most current findings about the role of epithelial cells in lung disease. Medical and graduate students, postdoctoral and clinical fellows, as well as clinicians interested in the mechanistic basis for lung disease will benefit from the books examination of principles of lung epithelium functions in physiological condition. Provides a single source of information on lung epithelial junctions and transporters Discusses of the role of the epithelium in lung homeostasis and disease Includes capsule summaries of main conclusions as well as highlights of future directions in the field Covers the mechanistic basis for lung disease for a range of audiences
This volume gives a comprehensive overview on the most relevant leukocyte and endothelial adhesion molecules. The chapters are written by leaders in the field and focus on the biology, structure, function, and regulation of adhesion molecules. Currently approved adhesion molecule-based therapies are reviewed and an outlook for future approaches is also provided. The book is of interest to clinicians and scientists from immunology, physiology, cancer research, rheumatology, allergology, infectious diseases, gastroenterology, pulmonology and cardiology.
Knowledge of the extracellular matrix (ECM) is essential to understand cellular differentiation, tissue development, and tissue remodeling. This volume of the series “Biology of Extracellular Matrix” provides a timely overview of the structure, regulation, and function of the major macromolecules that make up the extracellular matrix. It covers topics such as collagen types and assembly of collagen-containing suprastructures, basement membrane, fibronectin and other cell-adhesive glycoproteins, proteoglycans, microfibrils, elastin, fibulins and matricellular proteins, such as thrombospondin. It also explores the concept that ECM components together with their cell surface receptors can be viewed as intricate nano-devices that allow cells to physically organize their 3-D-environment. Further, the role of the ECM in human disease and pathogenesis is discussed as well as the use of model organisms in elucidating ECM function.
Integrins: Molecular and Biological Responses to the Extracellular Matrix will help basic, applied, and clinical researchers keep up with the explosion of literature on the integrin family of proteins. This volume extends material previously covered in Receptors for Extracellular Matrix. It addresses some of the most exciting areas of integrin biology, including the varied roles of integrins in cell division, differentiation, movement, wound healing, inflammation, thrombosis, osteoporosis, and cancer. Describes key aspects of integrin structure, function, and biology Covers collagen receptors, epithelial cell integrins, leukocyte integrins, platelet integrins, integrin signaling, and integrin antagonists Investigates the expression and role of integrins during development and in the cytoskeleton Includes the actions and influences of integrins in inflammation, thrombosis, and osteoporosis