Studies of the Structure and Function of the LDL Receptor-related Protein (LRP) PDF Download
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Author: Robert Charles Kowal
Publisher:
ISBN:
Category :
Languages : en
Pages : 390
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Book Description
Author: Robert Charles Kowal
Publisher:
ISBN:
Category :
Languages : en
Pages : 390
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Book Description
Author: Miklos Guttman
Publisher:
ISBN:
Category :
Languages : en
Pages : 184
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Book Description
The LDLR family of receptors mediates the uptake of lipoprotein particles, and is essential for cholesterol homeostasis. The LDL receptor-related protein 1 (LRP-1) mediates internalization of a large number of diverse ligands and is widely implicated in Alzheimer's disease. Clusters of complement-type ligand binding repeats (CRs) in the LDL receptor family are thought to mediate the interactions between these receptors and their various ligands. Apolipoprotein E, a key ligand for cholesterol homeostasis, has been shown to interact with LDLR, LRP and VLDLR, through these clusters. LDLR and VLDLR each contain a single ligand-binding repeat cluster, whereas LRP contains three large clusters of ligand binding repeats, each with ligand binding functions. In order to study smaller units of these ligand binding clusters we have engineered a new approach to express and refold complement repeat (CR) domains in E. coli. This successfully produced high yields of refolded protein with the benefit of inexpensive isotope labeling for NMR studies. We have expressed a subdomain of sLRP3 (CR16-18) that has previously been shown to recapitulate ligand binding to the isolated receptor binding portion of ApoE (residues 130-149). Binding experiments with the ApoE recognition region of LDLR (LA3-5) and CR16-18 showed that each CR could interact with ApoE(130-149) and that a conserved W25/D30 pair within each repeat appears critical for high affinity. The triple repeat LA3-5 showed the expected interaction with the lipid complexed ApoE(1-191)*DMPC, but surprisingly CR16-18 did not interact with this form of ApoE. To understand these differences in ApoE binding affinity, we introduced mutations of conserved residues from LA5 into CR18, and produced a CR16-18 variant capable of binding ApoE(1-191)*DMPC. This change cannot fully be accounted for by the interaction with ApoE's proposed receptor binding region, therefore we speculate that LA5 is recognizing a distinct epitope on ApoE that may only exist in the lipid bound form. The combination of avidity effects with this distinct recognition process likely governs the ApoE-LDL receptor interaction. Since even the strongest interaction between ApoE(130-149) and a single repeat (CR17) was relatively weak, we constructed a CR17-ApoE(130-149) fusion protein to stabilize the interface for structural studies. The structure revealed a motif seen previously in all ligand CR interactions, in which lysine residues of the ligand interact with the calcium binding site of the CR. Like many ligands of CRs ApoE(130-149) binds as a helix, but with an unexpected turn at H140. These studies also revealed that little structural rearrangement occurs within CR17 upon binding. In addition, dynamics measurements of the free and bound CR17 reveal that certain regions become more ordered, while others become less ordered upon binding. The cytoplasmic tail of LRP, containing two NPXY motifs, has been implicated in the onset of Alzheimer's disease. To examine the intracellular interactions of LRP, as well as to separate which proteins bind to each NPXY motif and their phosphorylation dependence, each NPXY motif microdomain was prepared in both phosphorylated and non-phosphorylated forms and used to probe rodent brain extracts for binding proteins. Proteins that bound specifically to the microdomains were identified by LC-MS/MS, and confirmed by western blot. Recombinant proteins were then tested for binding to each NPXY motif. The NPXY450-- (membrane distal) was found to interact with a large number of proteins, many of which only bound the tyrosine-phosphorylated form. This microdomain also bound a significant number of other proteins in the unphosphorylated state. Many of the interactions were later confirmed to be direct with recombinant proteins. The NPXY44--3 (membrane proximal) bound many fewer proteins and only to the phosphorylated form.
Author: Yoshiharu Takayama
Publisher: Springer Science & Business Media
ISBN: 9400724675
Category : Medical
Languages : en
Pages : 118
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Lactoferrin is an iron-binding glycoprotein belonging to the transferrin family. It acts as a defense in host animals against microbes and viruses, since it has a broad spectrum of antimicrobial and antiviral activities. Lactoferrin has been shown to regulate the growth and differentiation of many types of cells. The results of recent studies indicate that lactoferrin is a potent regulator of dermal fibroblasts, and promotes cutaneous wound healing. The collagen gel contraction, a model of wound contraction during wound healing process, and migration of human fibroblasts were enhanced by lactoferrin. LRP-1 (LDL Receptor related Protein-1) acts as a signaling receptor for lactoferrin that mediate fibroblast response to lactoferrin by activating ERK/MAPK signaling pathway. In addition, lactoferrin promotes biosynthesis of extracellular matrix (ECM) component such as type-I collagen and hyaluronan. Hyaluronan is a major component of ECM in connective tissue and promotes wound healing. The promoting effect of lactoferrin on hyaluronan production was accompanied by promotion of HAS2 (hyaluronan synthase 2) expression. These observations suggest that lactoferrin promotes the wound healing by providing an ECM that promotes fibroblast migration. Lactoferrin is also known for its anti-inflammatory and immune modulating properties. According to recent in vivo study, lactoferrin promotes wound repair by promoting the early inflammatory phase of wound healing. Based on this, recombinant human lactoferrin was subsequently tested clinically in a Phase II trial in patients with diabetic ulcers and was found to be effective. Lactoferrin should be further evaluated in patients with diabetic and other types of ulcers.
Author: Neale Ridgway
Publisher: Elsevier
ISBN: 0444634495
Category : Science
Languages : en
Pages : 625
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Book Description
Biochemistry of Lipids: Lipoproteins and Membranes, Volume Six, contains concise chapters that cover a wide spectrum of topics in the field of lipid biochemistry and cell biology. It provides an important bridge between broad-based biochemistry textbooks and more technical research publications, offering cohesive, foundational information. It is a valuable tool for advanced graduate students and researchers who are interested in exploring lipid biology in more detail, and includes overviews of lipid biology in both prokaryotes and eukaryotes, while also providing fundamental background on the subsequent descriptions of fatty acid synthesis, desaturation and elongation, and the pathways that lead the synthesis of complex phospholipids, sphingolipids, and their structural variants. Also covered are sections on how bioactive lipids are involved in cell signaling with an emphasis on disease implications and pathological consequences. Serves as a general reference book for scientists studying lipids, lipoproteins and membranes and as an advanced and up-to-date textbook for teachers and students who are familiar with the basic concepts of lipid biochemistry References from current literature will be included in each chapter to facilitate more in-depth study Key concepts are supported by figures and models to improve reader understanding Chapters provide historical perspective and current analysis of each topic
Author:
Publisher: ScholarlyEditions
ISBN: 1481614037
Category : Science
Languages : en
Pages : 56
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Book Description
Lipoprotein Receptors—Advances in Research and Application: 2012 Edition is a ScholarlyBrief™ that delivers timely, authoritative, comprehensive, and specialized information about Lipoprotein Receptors in a concise format. The editors have built Lipoprotein Receptors—Advances in Research and Application: 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Lipoprotein Receptors in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Lipoprotein Receptors—Advances in Research and Application: 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Author: Michael I. Gurr
Publisher: John Wiley & Sons
ISBN: 1405172703
Category : Medical
Languages : en
Pages : 339
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Book Description
Since the publication of the first edition of this successful and popular book in 1970, the subject of lipid biochemistry has evolved greatly and this fifth up-to-date and comprehensive edition includes much new and exciting information. Lipid Biochemistry, fifth edition has been largely re-written in a user-friendly way, with chapters containing special interest topic boxes, summary points and lists of suggested reading, further enhancing the accessibility and readability of this excellent text. Contents include abbreviations and definitions used in the study of lipids, routine analytical methods, fatty acid structure and metabolism, dietary lipids and lipids as energy stores, lipid transport, lipids in cellular structures and the metabolism of structural lipids. The book provides a most comprehensive treatment of the subject, making it essential reading for all those working with or studying lipids. Upper level students of biochemistry, biology, clinical subjects, nutrition and food science will find the contents of this book invaluable as a study aid, as will postgraduates specializing in the topics covered in the book. Professionals working in research in academia and industry, including personnel involved in food and nutrition research, new product formulation, special diet formulation (including nutraceuticals and functional foods) and other clinical aspects will find a vast wealth of information within the book's pages. Michael Gurr was a Visiting Professor in Human Nutrition at the University of Reading, UK and at Oxford Brookes University, UK. John Harwood is a Professor of Biochemistry at the School of Biosciences, Cardiff University, UK. Keith Frayn is a Professor of Human Metabolism at the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UK.
Author: Sangdun Choi
Publisher: Springer
ISBN: 9781493968008
Category : Medical
Languages : en
Pages : 6330
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Book Description
The second edition of this encyclopedia presents over 400 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities.
Author: Jean-Pierre Montmayeur
Publisher: CRC Press
ISBN: 1420067761
Category : Medical
Languages : en
Pages : 646
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Book Description
Presents the State-of-the-Art in Fat Taste TransductionA bite of cheese, a few potato chips, a delectable piece of bacon - a small taste of high-fat foods often draws you back for more. But why are fatty foods so appealing? Why do we crave them? Fat Detection: Taste, Texture, and Post Ingestive Effects covers the many factors responsible for the se
Author: Yona Keisari
Publisher: Springer Science & Business Media
ISBN: 030646831X
Category : Medical
Languages : en
Pages : 324
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Book Description
In recent years increased scientific attention has been given to immediate defense mechanisms based on non-clonal recognition of microbial components. These mechanisms constitute the innate immunity arm of the body s defense. Identification of pathogens by these mechanisms involves primarily receptors recognizing sugar moieties of various microorganisms. Innate immunity based mechanisms are essential for the existence of multicellular organisms. They are evolutionarily conserved and designed to provide immediate protection against microbial pathogens to eradicate infection. Activation of innate immunity is crucial for transition to specific immunity and for its orientation, and to assist the specific immune response in the recognition of pathogens and their destruction. Innate immunity is regularly involved in the arrest of bacterial, mycotic, viral and parasitic infections, giving the specific immune response time to become effective. It becomes critically essential in immunocompromised patients who fail to mount specific immune responses due to congenital or acquired immunodeficiencies as a result of chemotherapy, dialysis, immunosuppressive drugs, or HIV infection. The Innate Immunity arsenal constitutes polymorphonuclear and mononuclear phagocytes, mast cells, the complement system, Natural Killer cells, antimicrobial peptides, and presumably a subset of T lymphocytes with TCRl receptors.
Author: Richard B. M. Schasfoort
Publisher: Royal Society of Chemistry
ISBN: 1782627308
Category : Science
Languages : en
Pages : 555
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Book Description
Surface plasmon resonance (SPR) plays a dominant role in real-time interaction sensing of biomolecular binding events, this book provides a total system description including optics, fluidics and sensor surfaces for a wide researcher audience.
