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Mechanisms and Functions of Spatial Protein Quality Control
10.1146/annurev-biochem-060815-014616 2017-06-27 A healthy proteome is essential for cell survival. Protein misfolding is linked to a rapidly expanding list of human diseases, ranging from neurodegenerative diseases to aging and cancer. Many of these diseases are characterized by the accumulation of misfold... |
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Structural Studies of Amyloid Proteins at the Molecular Level
10.1146/annurev-biochem-061516-045104 2017-06-27 Dozens of proteins are known to convert to the aggregated amyloid state. These include fibrils associated with systemic and neurodegenerative diseases and cancer, functional amyloid fibrils in microorganisms and animals, and many denatured proteins. Amyloid f... |
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Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade
10.1146/annurev-biochem-061516-045115 2017-06-27 Peptides and proteins have been found to possess an inherent tendency to convert from their native functional states into intractable amyloid aggregates. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer an... |
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Protein Misfolding Diseases
10.1146/annurev-biochem-061516-044518 2017-06-27 The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally s... |
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At the Intersection of Chemistry, Biology, and Medicine
10.1146/annurev-biochem-110716-121241 2017-06-27 After an undergraduate degree in biology at Harvard, I started graduate school at The Rockefeller Institute for Medical Research in New York City in July 1965. I was attracted to the chemical side of biochemistry and joined Fritz Lipmann's large, hierarchical... |
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Reactive Oxygen Species and Neutrophil Function
10.1146/annurev-biochem-060815-014442 2016-06-13 Neutrophils are essential for killing bacteria and other microorganisms, and they also have a significant role in regulating the inflammatory response. Stimulated neutrophils activate their NADPH oxidase (NOX2) to generate large amounts of superoxide, which a... |
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Necroptosis and Inflammation
10.1146/annurev-biochem-060815-014830 2016-06-13 Necroptosis is a regulated form of necrosis, with the dying cell rupturing and releasing intracellular components that can trigger an innate immune response. Toll-like receptor 3 and 4 agonists, tumor necrosis factor, certain viral infections, or the T cell r... |
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Experimental Milestones in the Discovery of Molecular Chaperones as Polypeptide Unfolding Enzymes
10.1146/annurev-biochem-060815-014124 2016-06-13 Molecular chaperones control the cellular folding, assembly, unfolding, disassembly, translocation, activation, inactivation, disaggregation, and degradation of proteins. In 1989, groundbreaking experiments demonstrated that a purified chaperone can bind and ... |
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Mammalian Autophagy: How Does It Work?
10.1146/annurev-biochem-060815-014556 2016-06-13 Autophagy is a conserved intracellular pathway that delivers cytoplasmic contents to lysosomes for degradation via double-membrane autophagosomes. Autophagy substrates include organelles such as mitochondria, aggregate-prone proteins that cause neurodegenerat... |
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Mechanisms of Mitotic Spindle Assembly
10.1146/annurev-biochem-060815-014528 2016-06-13 Life depends on cell proliferation and the accurate segregation of chromosomes, which are mediated by the microtubule (MT)-based mitotic spindle and ∼200 essential MT-associated proteins. Yet, a mechanistic understanding of how the mitotic spindle is assemble... |