The Cell Membrane in the Steady State
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
A wide variety of protein molecules are associated with the cell membrane. They could be integral proteins that are part of the membrane, or peripheral proteins that temporarily attach either to the membrane or to the integral proteins. Integral proteins are of two types: Transmembrane proteins that extend across the membrane and form: (i) channels having aqueous pores, or “holes”, through which small molecules and ions can flow passively down an electrochemical potential gradient; (ii) ion transporters of various types that transport ions from one side of the membrane to the other, as explained in Section 2.3.Monotopic proteins, that is, proteins that are permanently attached to the cell membrane on only one side and do not extend across the membrane. These proteins are anchored to the membrane by having their hydrophobic regions extend into the fatty acid chain region of the membrane phospholipids.
Normal and Abnormal Development of the Biliary Tree
Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso in The Pathophysiology of Biliary Epithelia, 2020
ADPKD and its companion ADPLD are caused by mutations in the polycystin genes. These include PKD1 (chromosome 16p13.3), PKD2 (chromosome 4q13–23), and PKD2L (chromosome 10q25).94 These are integral transmembrane proteins with as yet uncharacterized functions, although a role in cell-cell and/or cell-matrix interactions is predicted on the basis of molecular sequences, localization data, and evidence of involvement in signaling.95 Homologies with voltage-activated and transient receptor potential ion channel proteins also implicate a direct role for polycystin molecules in ion transport.96 Numerous mutations have been described, most of which are expected to produce truncated proteins. There is debate as to whether the resultant decrease in levels of polycystins follows a model of dominant/negative function, in which a mutated form of polycystin would inactivate the normal polycystin, or by a cellular recessive mechanism. In support of the latter mechanism, Badenas et al97 have documented epithelial cell loss-of-heterozygosity (LOH) in 13.3% of 211 cysts analyzed from 7 patients with ADPKD (nine kidneys and one liver). A recently identified model of ADPKD develops spontaneously in the rat, and may also prove useful in elucidating the pathogenesis of this disorder.98 Of great interest is the fact that this rat model exhibits features of Caroli’s disease and congenital hepatic fibrosis as well.99
The cell
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella in Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
Proteins are also associated with the lipid bilayer and essentially float within it. Intrinsic, or transmembrane, proteins are embedded within and span the membrane. These proteins are like phospholipids in that they are amphipathic with the polar regions of the molecule extending beyond the lipid bilayer and the nonpolar region embedded within it. Extrinsic, or peripheral, proteins are found on either the internal or the external surface of the membrane (see Figure 1.1). These proteins are not amphipathic and do not associate with the internal region of the membrane. The membrane proteins provide a variety of important cellular functions by forming the following structures: ChannelsCarrier moleculesEnzymesChemical receptorsAntigens
Dipeptide-modified nanoparticles to facilitate oral docetaxel delivery: new insights into PepT1-mediated targeting strategy
Published in Drug Delivery, 2018
Yuqian Du, Chutong Tian, Menglin Wang, Di Huang, Wei Wei, Yan Liu, Lin Li, Bingjun Sun, Longfa Kou, Qiming Kan, Kexin Liu, Cong Luo, Jin Sun, Zhonggui He
Effort has been made to address these challenges. Among all the strategies, targeting delivery, especially membrane transporters are increasingly becoming striking targets for drug delivery (Li et al., 2013; Jiang et al., 2014; Tao et al., 2015; An et al., 2016; Tao et al., 2016; Zhu et al., 2016; Rosenblum et al., 2018). Transporters are integral transmembrane proteins and play a key role in the transport of ions, small molecules, and macromolecules across biomembrane (Luo et al., 2016; Kou et al., 2018). In general, transporters could be mainly categorized into two major super families including solute carriers (SLC) and ATP-binding cassette (ABC) depending on whether there is direct ATP consumption. Moreover, they usually prefer low molecule-weight substrates or analogs, which are easy to modify, more stable in gastrointestinal tract, less immunogenic, and more flexible when reaching the binding site due to less steric hindrance (Pereira et al., 2014).
Envelope proteins as antiviral drug target
Published in Journal of Drug Targeting, 2020
Jyoti Verma, Naidu Subbarao, Maitreyi S. Rajala
Viral fusion proteins are categorised into three classes depending upon their structural features. All the viral fusion proteins adopt a hairpin conformation in their final form. Class I fusion proteins form homotrimer in their pre- and post-fusion conformation with majority of alpha helices in their structure [21]. The enveloped viruses belonging to the families of Paramyxoviridae, Filoviridae, Orthomyxoviridae, Retroviridae and Coronaviridae have class I fusion glycoproteins [22]. They are alpha helical type I transmembrane proteins containing N- terminal (HR1 or HRN) and C- terminal (HR2 or HRC) heptad repeat. The fusion peptide is hydrophobic in nature located at the N-terminus buried within the protein core. Their pre-fusion conformation is thermodynamically stable coiled coil of three HR1 heptad repeats adjacent to the fusion peptide along with the HR2 heptad repeats. In the final stage of membrane fusion a post-fusion structure with a central N-terminal trimeric coiled coil upon which three C-terminal helices folds, eventually forms a six-helical bundle (6HB) [9,23,24].
Myosin light chain kinase regulates intestinal permeability of mucosal homeostasis in Crohn’s disease
Published in Expert Review of Clinical Immunology, 2020
Yiran Yao, Qi Feng, Jun Shen
TJ proteins are complex structures composed of more than 50 proteins, including a series of transmembrane proteins [68]. Transmembrane proteins mediate intercellular adhesion and seal the paracellular space. They include tetra-span and single-span proteins. Tetra-span proteins are composed of two extracellular loops and four transmembrane domains and include occludin, the claudin family, and tricellulin [69–71]. Plaque proteins, such as ZO-1, also have a role in the clustering and stabilization of transmembrane proteins. MLCK regulates the transmembrane proteins and associated proteins through its non-kinase activity to activate the TJ barrier, which controls intestinal permeability. The PAMR contributes to MLCK-dependent TJ regulation, which is the theoretical basis of targeting MLCK in a specific manner.
Related Knowledge Centers
- Beta Barrel
- Denaturation
- Detergent
- Integral Membrane Protein
- Transmembrane Domain
- Cell Membrane
- Membrane Transport Protein
- Protein Dynamics
- Protein Primary Structure
- Hydrophobicity Scales