Biochemical and Biophysical Approaches to Elucidate the Functional Mechanisms of Membrane Proteins

A special issue of Membranes (ISSN 2077-0375). This special issue belongs to the section "Biological Membrane Functions".

Deadline for manuscript submissions: closed (10 September 2022) | Viewed by 5163

Special Issue Editors


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Guest Editor
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA
Interests: molecular mechanisms of viral proteins in cellular membranes; membrane proteins from oncogenic viruses; membrane transporters of pathogenic bacteria; physiological function and malfunction of human proteins linked to cancer development

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Guest Editor
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA
Interests: rotary catalytic mechanism of ATP synthase; mechanism of polyspecific drug transport by P-glycoprotein; application of fluorescence spectroscopy to study membrane protein function

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Guest Editor
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA
Interests: membrane proteins from pathogenic viruses; molecular mechanisms of membrane proteins from human pathogens; biophysical approach for elucidation of membrane protein structure, function and conformational dynamics

Special Issue Information

Dear Colleagues,

Biological membranes determine the boundaries between cells and their surroundings, as well as compartmentalize the cells of higher organisms into organelles. These membranes have a complex organization, which is, in general, provided by the lipid bilayer and the proteins that reside in or are associated with the bilayer surface. Although the diversity of the lipid species determines, to a great extent, the properties of each particular membrane, proteins are indeed the major contributors to the specific physiological processes taking place in the membrane interior or at the periphery. Membrane proteins play fundamental roles in the physiology of living cells and multi-cell organisms. In addition to their physiological significance, numerous links have been identified between abnormal membrane protein function and life-threatening diseases, and the function and proliferation of proteins from human pathogens can be targeted pharmacologically. Therefore, in-depth understanding of the mechanisms of normal function and inhibition, as well as the pathology of these proteins, requires sufficient information about the coupling of structure and function.

This Special Issue aims to bring together the effort of scientists utilizing diverse biochemical and biophysical/structural biology approaches to elucidate membrane protein structure and conformational dynamics, as well as to develop assays to assess the functional activity of these proteins under close to native conditions of biological membranes and in the presence of physiological ligands or inhibitors. Manuscripts covering a broad range of structural and functional studies to characterize the physiological functions or disease-linked states of membrane proteins are welcome.

Suggested themes and article types for submissions:

In this Special Issue, original research articles, technical notes and reviews, including mini and systematic reviews, are welcome.

Research areas may include (but are not limited to) the following:

  • Integral and surface-associated membrane proteins with significant roles in cell physiology and diseases;
  • Molecular mechanisms of membrane transporters, channels and receptors;
  • Molecular mechanisms of membrane proteins from viruses and pathogenic bacteria;
  • Membrane remodeling proteins;
  • Protein–membrane recognition and association;
  • Protein–lipid interactions;
  • Development of biochemical and biophysical techniques to study membrane proteins in native or native-like environments.

We look forward to receiving your contributions.

Dr. Elka R. Georgieva
Dr. Joachim Weber
Dr. Saman Majeed
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Membranes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Membrane proteins
  • Membrane protein structure-function relationship
  • Membrane transport mechanism
  • Protein-lipid interactions
  • Protein folding and assembly in membranes
  • Membrane protein conformational dynamics
  • Membrane proteins functional assays
  • Protein-drug interaction

Published Papers (2 papers)

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Research

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21 pages, 3882 KiB  
Article
The Formation of β-Strand Nine (β9) in the Folding and Insertion of BamA from an Unfolded Form into Lipid Bilayers
by Sascha Herwig and Jörg H. Kleinschmidt
Membranes 2023, 13(2), 247; https://doi.org/10.3390/membranes13020247 - 19 Feb 2023
Cited by 1 | Viewed by 1441
Abstract
Transmembrane proteins span lipid bilayer membranes and serve essential functions in all living cells. Membrane-inserted domains are of either α-helical or β-barrel structure. Despite their biological importance, the biophysical mechanisms of the folding and insertion of proteins into membranes are not well [...] Read more.
Transmembrane proteins span lipid bilayer membranes and serve essential functions in all living cells. Membrane-inserted domains are of either α-helical or β-barrel structure. Despite their biological importance, the biophysical mechanisms of the folding and insertion of proteins into membranes are not well understood. While the relative composition of the secondary structure has been examined by circular dichroism spectroscopy in folding studies for several outer membrane proteins, it is currently not known how individual β-strands fold. Here, the folding and insertion of the β-barrel assembly machinery protein A (BamA) from the outer membrane of Escherichia coli into lipid bilayers were investigated, and the formation of strand nine (β9) of BamA was examined. Eight single-cysteine mutants of BamA were overexpressed and isolated in unfolded form in 8 M urea. In each of these mutants, one of the residues of strand β9, from R572 to V579, was replaced by a cysteine and labeled with the fluorophore IAEDANS for site-directed fluorescence spectroscopy. Upon urea-dilution, the mutants folded into the native structure and were inserted into lipid bilayers of dilauroylphosphatidylcholine, similar to wild-type BamA. An aqueous and a membrane-adsorbed folding intermediate of BamA could be identified by strong shifts in the intensity maxima of the IAEDANS fluorescence of the labeled mutants of BamA towards shorter wavelengths, even in the absence of lipid bilayers. The shifts were greatest for membrane-adsorbed mutants and smaller for the inserted, folded mutants or the aqueous intermediates. The spectra of the mutants V573C-, L575C-, G577C-, and V579C-BamA, facing the lipid bilayer, displayed stronger shifts than the spectra recorded for the mutants R572C-, N574C-, T576C-, and K578C-BamA, facing the β-barrel lumen, in both the membrane-adsorbed form and the folded, inserted form. This alternating pattern was neither observed for the IAEDANS spectra of the unfolded forms nor for the water-collapsed forms, indicating that strand β9 forms in a membrane-adsorbed folding intermediate of BamA. The combination of cysteine scanning mutagenesis and site-directed fluorescence labeling is shown to be a valuable tool in examining the local secondary structure formation of transmembrane proteins. Full article
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Review

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17 pages, 1894 KiB  
Review
Current Methods for Identifying Plasma Membrane Proteins as Cancer Biomarkers
by Edwin de Jong and Armagan Kocer
Membranes 2023, 13(4), 409; https://doi.org/10.3390/membranes13040409 - 05 Apr 2023
Cited by 4 | Viewed by 3046
Abstract
Plasma membrane proteins are a special class of biomolecules present on the cellular membrane. They provide the transport of ions, small molecules, and water in response to internal and external signals, define a cell’s immunological identity, and facilitate intra- and intercellular communication. Since [...] Read more.
Plasma membrane proteins are a special class of biomolecules present on the cellular membrane. They provide the transport of ions, small molecules, and water in response to internal and external signals, define a cell’s immunological identity, and facilitate intra- and intercellular communication. Since they are vital to almost all cellular functions, their mutants, or aberrant expression is linked to many diseases, including cancer, where they are a part of cancer cell-specific molecular signatures and phenotypes. In addition, their surface-exposed domains make them exciting biomarkers for targeting by imaging agents and drugs. This review looks at the challenges in identifying cancer-related cell membrane proteins and the current methodologies that solve most of the challenges. We classified the methodologies as biased, i.e., search cells for the presence of already known membrane proteins. Second, we discuss the unbiased methods that can identify proteins without prior knowledge of what they are. Finally, we discuss the potential impact of membrane proteins on the early detection and treatment of cancer. Full article
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