Membrane proteins are the general term for proteins that can bind or integrate into membranes of cells or organelles. They are surrounded by a phospholipid bilayer. Membrane proteins are indispensable components of biological membranes and they constitute the receptors of various nerve signaling molecules, hormones and other substrates, the transmembrane channels of various ions and the transport channels of substances and etc. Thus, they are also the main undertaker of biological membranes functions. Owing to their favorable location in the cell membrane and their diverse functions, membrane protein has become a research hotspot, and has become an important target of drug research and development, which has huge potential market value and medical significance.
Based on the nature of their association with the membrane, membrane proteins have been divided into two major classes of peripheral membrane proteins and integral membrane proteins, in which integral membrane proteins can be further subdivided into two subclasses of anchored proteins and transmembrane proteins. Peripheral membrane proteins are generally not integrated into the hydrophobic domain of the membrane lipid bilayer interior. All of the mass of the peripheral protein is outside the hydrophobic interior of the membrane. Anchored proteins bury a portion of their mass in the hydrophobic interior of the lipid bilayer. Transmembrane proteins span the lipid bilayer and some portion of the mass of the protein appears on both sides of the membrane [1]. Transmembrane proteins are the most important class of membrane proteins and account for about 70% to 80% of the total membrane protein. In addition, transmembrane proteins perform many physiological functions and are an ideal target for many drugs. Therefore, the research of membrane proteins mainly focuses on transmembrane proteins.
Fig. 1. Representation of membrane protein: peripheral membrane proteins, anchored proteins and transmembrane proteins.
Membrane proteins play an irreplaceable role in transmembrane material transport, energy conversion, signal transduction, membrane homeostasis maintenance, etc. Specifically, they perform most important cellular functions, including oxidative phosphorylation and proton pumping, ATP synthesis, transport of metabolites, intra- and inter cellular signaling, membrane fusion and communication between cell compartments, the biosynthesis of many compounds including lipids, steroid hormones, and their derivatives, and the breakdown of xenobiotics and internal metabolites. And developmental processes, including cell motility, adhesion, recognition, neuronal patterning, and many other critical events, are also conducted by membrane proteins [2].
![Fig. 2. Example of membrane protein mediated signal transduction [3].](/upload/image/2-2-membrane-proteins-3.jpg)
Fig. 2. Example of membrane protein mediated signal transduction [3].
The abnormal function of membrane protein is associated with many diseases heart disease such as cystic fibrosis, depression, obesity, cancer and many others. So, membrane protein as an important drug target has great application in drug development. Previous reports indicate that membrane proteins account for >60% of the current drug targets. Nowadays, drugs based on membrane protein target have been developed for many diseases such as asthma, hypertension, rhinitis, schizophrenia, pain, migraine and prostate cancer. In addition, the immunogens of some viruses in nature are membrane proteins, such as the COVID-19 spike protein, influenza virus hemagglutinin, HIV envelope glycoprotein, respiratory syncytial virus fusion protein, etc. Therefore, membrane proteins are also used in vaccine development. Moreover, membrane proteins also have certain applications in the field of antibody discovery and biological assays.
Alfa Chemistry focuses on the development of membrane proteins, especially transmembrane protein products, with the aim of providing raw materials for early drug development. To assist in drug research of membrane protein targets and meet the requirements of different application scenarios, Alfa Chemistry has built three technology platforms for the R&D and production of membrane proteins (detergent platform, nanodisc platform and virus like particles (VLP) platform) based on our powerful detergents, nanodisc and membrane protein research technologies. At present, Alfa Chemistry effectively manufactures a large number of membrane proteins by these platforms, including CD20, Claudin-6, Claudin-9, Claudin-18.1, Claudin-18.2, CD133, GPRC5D, CXCR4, CCR5, CCR8, SSTR2, etc. Please feel free to contact us for more information.
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