Tryptophan, an Amino-Acid Endowed with Unique Properties and Its Many Roles in Membrane Proteins

Tryptophan is an aromatic amino acid with unique physico-chemical properties. It is often encountered in membrane proteins, especially at the level of the water/bilayer interface. It plays a role in membrane protein stabilization, anchoring and orientation in lipid bilayers. It has a hydrophobic character but can also engage in many types of interactions, such as π–cation or hydrogen bonds. In this review, we give an overview of the role of tryptophan in membrane proteins and a more detailed description of the underlying noncovalent interactions it can engage in with membrane partners.

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A Comprehensive Computational Study of Amino Acid Interactions in Membrane Proteins

10.1101/617498 ◽

2019 ◽

Author(s):

Mame Ndew Mbaye ◽

Qingzhen Hou ◽

Sankar Basu ◽

Fabian Teheux ◽

Fabrizio Pucci ◽

...

Keyword(s):

Amino Acid ◽

Membrane Proteins ◽

Membrane Protein ◽

Computational Study ◽

Globular Proteins ◽

Protein Stabilization ◽

Energy Functions ◽

Hydrophobic Residues ◽

Polar Residues ◽

Transmembrane Regions

AbstractTransmembrane proteins play a fundamental role in a wide series of biological processes but, despite their importance, they are less studied than globular proteins, essentially because their embedding in lipid membranes hampers their experimental characterization. In this paper, we improved our understanding of their structural stability through the development of new knowledge-based energy functions describing amino acid pair interactions that prevail in the transmembrane and extramembrane regions of membrane proteins. The comparison of these potentials and those derived from globular proteins yields an objective view of the relative strength of amino acid interactions in the different protein environments, and their role in protein stabilization. Separate potentials were also derived from α-helical and β-barrel transmembrane regions to investigate possible dissimilarities. We found that, in extramembrane regions, hydrophobic residues are less frequent but interactions between aromatic and aliphatic amino acids as well as aromatic-sulfur interactions contribute more to stability. In transmembrane regions, polar residues are less abundant but interactions between residues of equal or opposite charges or non-charged polar residues as well as anion-π interactions appear stronger. This shows indirectly the preference of the water and lipid molecules to interact with polar and hydrophobic residues, respectively. We applied these new energy functions to predict whether a residue is located in the trans- or extramembrane region, and obtained an AUC score of 83% in cross validation, which demonstrates their accuracy. As their application is, moreover, extremely fast, they are optimal instruments for membrane protein design and large-scale investigations of membrane protein stability.

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The Role of HIV-1 gp41 Glycoprotein in Infectious Tropism Inferred from Physico-Chemical Properties of its Amino Acid Sequence

10.1063/1.2356440 ◽

2006 ◽

Author(s):

E. Figueroa ◽

C. Villarreal ◽

L. Huerta ◽

G. Cocho

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Chemical Properties ◽

Physico Chemical ◽

Hiv 1

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Lipid Transporters Beam Signals from Cell Membranes

Membranes ◽

10.3390/membranes11080562 ◽

2021 ◽

Vol 11 (8) ◽

pp. 562

Author(s):

Miliça Ristovski ◽

Danny Farhat ◽

Shelly Ellaine M. Bancud ◽

Jyh-Yeuan Lee

Keyword(s):

Membrane Proteins ◽

Lipid Bilayers ◽

Lipid Composition ◽

Structural Integrity ◽

Current Knowledge ◽

Integral Membrane Proteins ◽

Cellular Membranes ◽

Cytoplasmic Proteins ◽

Lipid Transporters

Lipid composition in cellular membranes plays an important role in maintaining the structural integrity of cells and in regulating cellular signaling that controls functions of both membrane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transporters, two integral membrane proteins, are known to contribute to lipid translocation across the lipid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membranes in regulating cell signaling and how lipid transporters participate this process.

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Occurrence of drug target residues within decantation tank sediments: a good clue to assess their historical excretion?

Sustainable Environment Research ◽

10.1186/s42834-021-00092-w ◽

2021 ◽

Vol 31 (1) ◽

Author(s):

Thomas Thiebault ◽

Laëtitia Fougère ◽

Anaëlle Simonneau ◽

Emilie Destandau ◽

Claude Le Milbeau ◽

...

Keyword(s):

Drug Target ◽

Chemical Properties ◽

Deposition Process ◽

Drug Consumption ◽

Organic Layers ◽

Sewer Systems ◽

Physico Chemical ◽

Deep Underground ◽

Deposition Processes

AbstractThis study investigated the potential of sediments accumulated in sewer systems to record human activities through the occurrence of drug target residues (DTR). The installation studied is 17 m deep underground decantation tank that traps the coarse fractions of a unitary sewer system (northern part of Orléans, France), collecting both stormwater and wastewater. The sediments deposited in this tank could constitute a nonesuch opportunity to study the historical evolution of illicit and licit drug consumption in the catchment, however, the deposition processes and the record of DTRs remain largely unknown at present. Five cores were acquired from 2015 to 2017. One hundred fifty-two sediment samples were extracted using a mixture of ultra-pure water:methanol (1:1) prior to analysis of the extracts by high-pressure liquid chromatography coupled to tandem mass spectrometry. Several classical sedimentological analyses such as total organic carbon, facies description and granulometry were also performed on these samples, in order to understand the most important factors (e.g., physico-chemical properties of the DTRs, solid type, assumed load in wastewater) impacting their deposition.The key role of the speciation of DTRs was highlighted by the higher contents in neutral and anionic DTRs in organic layers, whereas only cationic DTRs were found in mineral layers. The considerable modifications in the sediments’ properties, generated by distinct origins (i.e., stormwater or wastewater), are therefore the most important drivers that must be taken into account when back-calculating the historical patterns of drug consumption from their DTR concentrations in decantation tank sediments. Further research remains necessary to fully understand the deposition process, but this study provides new clues explaining these temporal evolutions.

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Membrane Protein Stabilization Strategies for Structural and Functional Studies

Membranes ◽

10.3390/membranes11020155 ◽

2021 ◽

Vol 11 (2) ◽

pp. 155

Author(s):

Ekaitz Errasti-Murugarren ◽

Paola Bartoccioni ◽

Manuel Palacín

Keyword(s):

Membrane Proteins ◽

Membrane Protein ◽

Lipid Membrane ◽

Protein Stabilization ◽

New Drugs ◽

Cell Physiology ◽

Protein Preparation ◽

Functional Studies ◽

Membrane Protein Stability ◽

Druggable Targets

Accounting for nearly two-thirds of known druggable targets, membrane proteins are highly relevant for cell physiology and pharmacology. In this regard, the structural determination of pharmacologically relevant targets would facilitate the intelligent design of new drugs. The structural biology of membrane proteins is a field experiencing significant growth as a result of the development of new strategies for structure determination. However, membrane protein preparation for structural studies continues to be a limiting step in many cases due to the inherent instability of these molecules in non-native membrane environments. This review describes the approaches that have been developed to improve membrane protein stability. Membrane protein mutagenesis, detergent selection, lipid membrane mimics, antibodies, and ligands are described in this review as approaches to facilitate the production of purified and stable membrane proteins of interest for structural and functional studies.

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The role of membrane surface charge and solute physico-chemical properties in the rejection of organic acids by NF membranes

Journal of Membrane Science ◽

10.1016/j.memsci.2004.09.041 ◽

2005 ◽

Vol 249 (1-2) ◽

pp. 227-234 ◽

Cited By ~ 211

Author(s):

Christopher Bellona ◽

Jörg E. Drewes

Keyword(s):

Organic Acids ◽

Surface Charge ◽

Membrane Surface ◽

Chemical Properties ◽

Physico Chemical ◽

Membrane Surface Charge

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NCU-G1 is a highly glycosylated integral membrane protein of the lysosome

Biochemical Journal ◽

10.1042/bj20090567 ◽

2009 ◽

Vol 422 (1) ◽

pp. 83-90 ◽

Cited By ~ 17

Author(s):

Oliver Schieweck ◽

Markus Damme ◽

Bernd Schröder ◽

Andrej Hasilik ◽

Bernhard Schmidt ◽

...

Keyword(s):

Amino Acid ◽

Membrane Proteins ◽

Membrane Protein ◽

Mouse Liver ◽

Lysosomal Membrane ◽

Molecular Forms ◽

Type I ◽

Calculated Molecular Mass ◽

Sorting Motif ◽

Lysosomal Membrane Proteins

Until recently, a modest number of approx. 40 lysosomal membrane proteins had been identified and even fewer were characterized in their function. In a proteomic study, using lysosomal membranes from human placenta we identified several candidate lysosomal membrane proteins and proved the lysosomal localization of two of them. In the present study, we demonstrate the lysosomal localization of the mouse orthologue of the human C1orf85 protein, which has been termed kidney-predominant protein NCU-G1 (GenBank® accession number: AB027141). NCU-G1 encodes a 404 amino acid protein with a calculated molecular mass of 39 kDa. The bioinformatics analysis of its amino acid sequence suggests it is a type I transmembrane protein containing a single tyrosine-based consensus lysosomal sorting motif at position 400 within the 12-residue C-terminal tail. Its lysosomal localization was confirmed using immunofluorescence with a C-terminally His-tagged NCU-G1 and the lysosomal marker LAMP-1 (lysosome-associated membrane protein-1) as a reference, and by subcellular fractionation of mouse liver after a tyloxapol-induced density shift of the lysosomal fraction using an anti-NCU-G1 antiserum. In transiently transfected HT1080 and HeLa cells, the His-tagged NCU-G1 was detected in two molecular forms with apparent protein sizes of 70 and 80 kDa, and in mouse liver the endogenous wild-type NCU-G1 was detected as a 75 kDa protein. The remarkable difference between the apparent and the calculated molecular masses of NCU-G1 was shown, by digesting the protein with N-glycosidase F, to be due to an extensive glycosylation. The lysosomal localization was impaired by mutational replacement of an alanine residue for the tyrosine residue within the putative sorting motif.

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