China
Africa
Explore chapters and articles related to this topic
Finding a Target
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Other membrane proteins are located within the cytoplasm; attached to the cell membrane by means of covalent bonding with fatty acid chains, while other membrane proteins are entirely exposed to the extracellular medium and are attached to the cell membrane by covalent bonds to specific oligosaccharides. Additional proteins may be bound to these integral membrane proteins by non-covalent interactions and are known as peripheral membrane proteins. These types of proteins have different functions. The transmembrane proteins are often involved in molecular transport across cell membranes. Extrinsic proteins serve as cell signalling receptors.
Structures and Properties of Self-Assembled Phospholipids in Excess Water
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
The integral membrane proteins or glycoproteins usually have one or more segments of hydrophobic amino acid residues penetrating the lipid bilayer.6 Within the lipid bilayer, these residues are almost exclusively arranged as a-helices with an orientation nearly perpendicular to the bilayer surface. The dynamics and mobility of these bilayer-spanning proteins or glycoproteins must, therefore, be subject to modulation by the organization and polymorphism of the lipid bilayer. Consequently, the functional states of bilayer-spanning proteins or glycoproteins in biological membranes may be correlated with the physical state of the lipid bilayer. The function of lipid bilayers should, therefore, be considered not only to serve as a barrier separating two aqueous compartments, but also to modulate the activity of membrane proteins. Hence, studies of phospholipids and other membrane lipids in the form of a bilayer are of great importance in understanding the functional control of bilayer-spanning proteins in biological membranes and for providing basic information explaining the dynamic regulation of membrane activities in general.
Atomic Force Microscopy of Biomembranes
Published in Qiu-Xing Jiang, New Techniques for Studying Biomembranes, 2020
Yi Ruan, Lorena Redondo-Morata, Simon Scheuring
Integral membrane proteins, also known as transmembrane proteins, are embedded within the bilayer membranes of a cell, and are generally responsible for signal transduction, compound transport or channeling, etc. Importantly, most transmembrane proteins function with a conformational change as indicated by X-ray structures. However, a direct visualization of the conformational changes of a transmembrane protein remained elusive in static structures, nor can dynamic parameters be deduced from them. HS-AFM provides a unique method to probe membrane proteins in native-like lipid membranes. With the recent developments, it enables us to control the environment and resolve the details of conformational change of membrane proteins in real time.
Open resources for chemical probes and their implications for future drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Esra Balıkçı, Anne-Sophie M. C. Marques, Jesper S. Hansen, Kilian V. M. Huber
SLCs comprise the largest family of transporters in the human genome with more than 450 members, currently divided into 66 different families based on either sequence, fold, or functional similarity [64]. These proteins are integral membrane proteins residing in cellular membranes with more than half localized to the plasma membrane [65]. SLCs transport a wide range of small molecules, including metabolites, nutrients, amino acids, hormones, metal ions, as well as small molecule drugs across cell membranes [65]. The spectrum of on average≥100 different types of SLCs produced by a given cell defines the intracellular composition of solutes such as metabolites and drugs [66]. Not surprisingly, many SLCs have been implicated in common diseases such as cancer, diabetes, heart disease, Alzheimer’s, and neuropsychiatric disorders. Hence, SLCs are emerging as a superfamily of highly disease-relevant and pharmacologically tractable proteins. The importance of SLCs as pharmacological targets is demonstrated by the fact that the most successful therapy for depression includes blocking serotonin reuptake with fluoxetine (Prozac), which works as an antagonist of the serotonin transporter SLC6A4 [67].
Protective role of PERK-eIF2α-ATF4 pathway in chronic renal failure induced injury of rat hippocampal neurons
Published in International Journal of Neuroscience, 2023
Qi Chen, Jingjing Min, Ming Zhu, Zhanqin Shi, Pingping Chen, Lingyan Ren, Xiaoyi Wang
The endoplasmic reticulum is one of the most important organelles in eukaryotic cells. It is not only the site for protein translation and synthesis as well as calcium ion storage, but also a participant in the transmission and processing of various cell signals. In addition, one of the major functions of the endoplasmic reticulum is to serve as a site for synthesizing secretory and integral membrane proteins.5,6 When cells are stimulated by hypoxia, an imbalance of calcium ions or a change in their concentration occurs in the internal environment, accompanied with the accumulation of some unfolded proteins in the endoplasmic reticulum, resulting in an imbalance between the structure and function of the endoplasmic reticulum. At this time, the corresponding signal pathway is activated to further trigger the endoplasmic reticulum stress (ERS) response.7 Unfolded protein response activation can be triggered in the following three ways: (1) inhibition of protein translation to prevent the production of more folded proteins; (2) induction of the folding of unfolded proteins by the endoplasmic reticulum chaperone; (3) activation of endoplasmic reticulum associated degradation pathways to remove unfolded proteins accumulated in the endoplasmic reticulum.8 However, under prolonged or severe stress, the unfolded protein response initiates programmed cell death.
Cell-cell junctions: structure and regulation in physiology and pathology
Published in Tissue Barriers, 2021
Mir S. Adil, S. Priya Narayanan, Payaningal R. Somanath
The zona occludens (ZO) family includes ZO-1, ZO-2, and ZO-3, which contain three PDZ domains (PDZ1, PDZ2, PDZ3) belong to the membrane-associated guanylate kinase (MAGUK) family.75 ZO-1 was the first identified TJ protein in the year 1986.33 It is a scaffolding protein that provides the structural basis for the assembly of multiprotein complexes at the cytoplasmic surface of intercellular junctions.76 Besides, it connects the integral membrane proteins with the filamentous cytoskeleton.21 The knockout of ZO-1 was shown to be lethal for mouse embryos around the mid-gestation period.21,76 ZO-2 is another ZO protein that is reported to be involved in cell growth and proliferation.21 The indirect interaction of ZO proteins with the cytoskeleton involves several actin-binding proteins including cortactin, alpha-catenin, protein 4.1 R, the Ras target AF6/afadin as well as the actin- and myosin-binding proteins cingulin and Shroom.21