Recent advances in the electrochemistry and spectroelectrochemistry of membrane proteins

2013 ◽  
Vol 394 (5) ◽  
pp. 593-609 ◽  
Author(s):  
Frederic Melin ◽  
Petra Hellwig

Abstract Integral membrane proteins are encountered in fundamental natural processes, such as photosynthesis and respiration. The relation between the structure of the proteins and their function and dynamics are still not clear in most cases. Once fully understood, these processes could ultimately help researchers to develop alternative methods for producing energy, either from light or biomass. They could also lead to more efficient antibiotics, which would selectively inhibit a specific membrane protein of pathogenic bacteria. Since the chemical reactions involved in both photosynthesis and respiration are redox reactions, electrochemical methods can play a considerable role in uncovering their mechanisms. The electrochemical characterization of membrane proteins is, however, quite challenging. An overview on the techniques used for the characterization of membrane proteins, including classical approaches such as voltammetry and spectroelectrochemistry, and recent developments, such as their combination with surface-enhanced techniques is given.

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1246
Author(s):  
Nhi T. Tran ◽  
Frédéric Mentink-Vigier ◽  
Joanna R. Long

While atomic scale structural and dynamic information are hallmarks of nuclear magnetic resonance (NMR) methodologies, sensitivity is a fundamental limitation in NMR studies. Fully exploiting NMR capabilities to study membrane proteins is further hampered by their dilution within biological membranes. Recent developments in dynamic nuclear polarization (DNP), which can transfer the relatively high polarization of unpaired electrons to nuclear spins, show promise for overcoming the sensitivity bottleneck and enabling NMR characterization of membrane proteins under native-like conditions. Here we discuss fundamental aspects of DNP-enhanced solid-state NMR spectroscopy, experimental details relevant to the study of lipid assemblies and incorporated proteins, and sensitivity gains which can be realized in biomembrane-based samples. We also present unique insights which can be gained from DNP measurements and prospects for further development of the technique for elucidating structures and orientations of membrane proteins in native lipid environments.


2000 ◽  
Vol 63 (6) ◽  
pp. 1839-1847 ◽  
Author(s):  
Nancy P. Haden ◽  
John R. Hickox ◽  
C. Scott Whisnant ◽  
Daniel M. Hardy

Author(s):  
L. M. Marshall

A human erythroleukemic cell line, metabolically blocked in a late stage of erythropoiesis, becomes capable of differentiation along the normal pathway when grown in the presence of hemin. This process is characterized by hemoglobin synthesis followed by rearrangement of the plasma membrane proteins and culminates in asymmetrical cytokinesis in the absence of nuclear division. A reticulocyte-like cell buds from the nucleus-containing parent cell after erythrocyte specific membrane proteins have been sequestered into its membrane. In this process the parent cell faces two obstacles. First, to organize its erythrocyte specific proteins at one pole of the cell for inclusion in the reticulocyte; second, to reduce or abolish membrane protein turnover since hemoglobin is virtually the only protein being synthesized at this stage. A means of achieving redistribution and cessation of turnover could involve movement of membrane proteins by a directional lipid flow. Generation of a lipid flow towards one pole and accumulation of erythrocyte-specific membrane proteins could be achieved by clathrin coated pits which are implicated in membrane endocytosis, intracellular transport and turnover. In non-differentiating cells, membrane proteins are turned over and are random in surface distribution. If, however, the erythrocyte specific proteins in differentiating cells were excluded from endocytosing coated pits, not only would their turnover cease, but they would also tend to drift towards and collect at the site of endocytosis. This hypothesis requires that different protein species are endocytosed by the coated vesicles in non-differentiating than by differentiating cells.


2001 ◽  
Vol 66 (9) ◽  
pp. 1315-1340 ◽  
Author(s):  
Vladimir J. Balcar ◽  
Akiko Takamoto ◽  
Yukio Yoneda

The review highlights the landmark studies leading from the discovery and initial characterization of the Na+-dependent "high affinity" uptake in the mammalian brain to the cloning of individual transporters and the subsequent expansion of the field into the realm of molecular biology. When the data and hypotheses from 1970's are confronted with the recent developments in the field, we can conclude that the suggestions made nearly thirty years ago were essentially correct: the uptake, mediated by an active transport into neurons and glial cells, serves to control the extracellular concentrations of L-glutamate and prevents the neurotoxicity. The modern techniques of molecular biology may have provided additional data on the nature and location of the transporters but the classical neurochemical approach, using structural analogues of glutamate designed as specific inhibitors or substrates for glutamate transport, has been crucial for the investigations of particular roles that glutamate transport might play in health and disease. Analysis of recent structure/activity data presented in this review has yielded a novel insight into the pharmacological characteristics of L-glutamate transport, suggesting existence of additional heterogeneity in the system, beyond that so far discovered by molecular genetics. More compounds that specifically interact with individual glutamate transporters are urgently needed for more detailed investigations of neurochemical characteristics of glutamatergic transport and its integration into the glutamatergic synapses in the central nervous system. A review with 162 references.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1778
Author(s):  
Pakhuri Mehta ◽  
Przemysław Miszta ◽  
Sławomir Filipek

The recent developments of fast reliable docking, virtual screening and other algorithms gave rise to discovery of many novel ligands of histamine receptors that could be used for treatment of allergic inflammatory disorders, central nervous system pathologies, pain, cancer and obesity. Furthermore, the pharmacological profiles of ligands clearly indicate that these receptors may be considered as targets not only for selective but also for multi-target drugs that could be used for treatment of complex disorders such as Alzheimer’s disease. Therefore, analysis of protein-ligand recognition in the binding site of histamine receptors and also other molecular targets has become a valuable tool in drug design toolkit. This review covers the period 2014–2020 in the field of theoretical investigations of histamine receptors mostly based on molecular modeling as well as the experimental characterization of novel ligands of these receptors.


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