Article
Microbiology
Sunyia Hussain, Janine H. Peterson, Harris D. Bernstein
Summary: The assembly of trimeric porins involves a stepwise process that requires the presence of the Bam complex and LPS. The interaction with LPS is not only essential for trimerization but also for the productive insertion of individual subunits into the lipid bilayer.
Review
Microbiology
Matthew Thomas Doyle, Harris D. Bernstein
Summary: The Omp85 protein superfamily is a group of proteins found in the outer membrane of gram-negative bacteria and bacterial-origin eukaryotic organelles. These proteins are involved in both membrane insertion and translocation of proteins across the outer membrane. Recent studies have uncovered new insights into the functions of these proteins, particularly the well-studied member BamA, which is essential for bacterial barrel assembly and has potential implications for antibiotic development.
ANNUAL REVIEW OF MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Simen Hermansen, David Ryoo, Marcella Orwick-Rydmark, Athanasios Saragliadis, James C. Gumbart, Dirk Linke
Summary: The outer membrane of Gram-negative bacteria acts as an additional diffusion barrier for solutes and nutrients. Outer membrane proteins (OMPs) with large loops protruding into the extracellular environment have potential applications in biotechnology and therapy. This study quantifies the effects of loop insertions on OMP folding and stability using the small outer membrane protein OmpX as a model system. The results show that the length and hydrophobicity of insertions affect OMP folding, and different constructs can fold both in vitro and in their native environment. These findings will improve the design and efficiency of recombinant OMPs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Multidisciplinary Sciences
Ashton N. Combs, Thomas J. Silhavy
Summary: This study reveals a novel role for the periplasmic chaperone Skp in the folding of outer membrane proteins (OMPs) in gram-negative bacteria. Skp removes membrane-integration-defective OMP substrates from the beta-barrel assembly machine (Bam) complex, allowing for clearance of stalled Bam-OMP complexes. Furthermore, Skp acts as an adaptor protein to facilitate the degradation of defective OMP substrates by the periplasmic protease DegP. These findings highlight the importance of Skp in ensuring efficient beta-barrel folding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Yindi Chu, Zhe Wang, Sebastian Weigold, Derrick Norrell, Enguo Fan
Summary: Research shows that a single TtOmp85 protein can replace the collective function of the five subunits constituting the E. coli BAM, providing new insights into the search for the primitive form of a functional BAM.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Microbiology
Xu Wang, Janine H. Peterson, Harris D. Bernstein
Summary: This study identified two parallel mechanisms for the assembly of outer membrane proteins in Gram-negative bacteria, involving the beta signal and SurA. It challenges the view that periplasmic chaperones are redundant, suggesting they have specialized roles in OMP targeting and quality control.
Article
Biochemistry & Molecular Biology
Dung T. Huynh, Wouter S. P. Jong, Gregory M. Koningstein, Peter van Ulsen, Joen Luirink
Summary: Ct-MOMP, a promising subunit-based vaccine candidate, is difficult to express in its native structure in E. coli outer membrane. Co-expression of the Bam complex improved the expression and localization of recombinant Ct-MOMP, leading to correct folding and assembly into a beta-barrel conformation at the cell surface.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Cosmin L. Pocanschi, Joerg H. Kleinschmidt
Summary: Extraction of integral membrane proteins into detergents for structural and functional studies often results in protein instability. This study compares the stability of FhuA and its mutant form, FhuA Delta 5-160, in detergent and lipid bilayer conditions. The results show that reconstitution into lipid bilayers increases the stability of FhuA and raises the unfolding temperature of the protein.
JOURNAL OF MEMBRANE BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Eve E. Weatherill, Monifa A. Fahie, David P. Marshall, Rachel A. Andvig, Matthew R. Cheetham, Min Chen, Mark Wallace
Summary: Compared to globular proteins, the folding and insertion of beta-barrel membrane proteins are slow but rapid, occurring within seconds upon arrival at the membrane interface. This combination of infrequent yet fast folding events resolves the apparent contradiction between slow ensemble kinetics and typical biomolecular folding timescales.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Infectious Diseases
Claire Overly Cottom, Robert Stephenson, Lindsey Wilson, Nicholas Noinaj
Summary: The emergence of multidrug resistance in bacterial pathogens poses a global threat to human health, but the discovery of new antibiotics has not kept pace with this alarming trend. Recent approaches to antibiotic discovery have expanded to target essential surface receptors and protein complexes, including the beta-barrel assembly machinery (BAM) responsible for the biogenesis of outer membrane proteins in Gram-negative bacteria. In this review, we highlight the importance of BAM as a promising therapeutic target and discuss recent studies on compounds and vaccines targeting BAM across various bacteria, sparking ongoing research and interest in BAM for combating multidrug resistance.
Article
Biochemistry & Molecular Biology
Pankaj B. Tiwari, Radhakrishnan Mahalakshmi
Summary: The study reveals that BamA is a substrate-independent promiscuous molecular chaperone, assisting unfolded OMP to overcome the kinetic barrier in assembly and accelerate folding. The primary sequence of OMP remains a vital determining factor in its assembly rate.
Article
Biochemistry & Molecular Biology
Sina Kordes, Sergio Romero-Romero, Leonie Lutz, Birte Hoecker
Summary: This study investigates the effects of introducing salt bridge clusters into different protein structures on their stability and conformational stability, revealing that salt bridge clusters can have varying impacts on the conformational stability of proteins.
Article
Biochemistry & Molecular Biology
Sascha Herwig, Joerg H. Kleinschmidt
Summary: Transmembrane proteins play essential roles in all living cells, but the folding and insertion mechanisms of these proteins into membranes are not well understood. In this study, the folding and insertion process of BamA protein into lipid bilayers was investigated, and the formation of beta(9) strand was examined. The results showed that the beta(9) strand forms in a membrane-adsorbed folding intermediate of BamA. This study provides valuable insights into the local secondary structure formation of transmembrane proteins.
Article
Microbiology
Janine H. Peterson, Matthew Thomas Doyle, Harris D. Bernstein
Summary: Several antibacterial compounds have been found to inhibit BAM function through different mechanisms, affecting the biogenesis of outer membrane proteins in Gram-negative bacteria. These findings not only provide important insights for developing novel broad-spectrum antibiotics, but also valuable tools for future studies on BAM function.
Article
Multidisciplinary Sciences
Neharika Chamachi, Andreas Hartmann, Mai Quynh Ma, Anna Svirina, Georg Krainer, Michael Schlierf
Summary: This study investigates the essential role of periplasmic chaperones, 17-kilodalton protein (Skp) and survival factor A (SurA), in outer membrane protein (OMP) biogenesis. The researchers use single-molecule fluorescence spectroscopy to analyze the conformational dynamics and thermodynamics of Skp and SurA binding to unfolded OmpX and study their disaggre-gase activities. The findings provide insights into the multifaceted functionalities of Skp and SurA and shed light on the balance between conformational flexibility and underlying ener-getics in aiding chaperone action during OMP biogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Deepti Chaturvedi, Radhakrishnan Mahalakshmi
Review
Biochemistry & Molecular Biology
Radhakrishnan Mahalakshmi
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2019)
Article
Physiology
Ankit Gupta, Radhakrishnan Mahalakshmi
JOURNAL OF GENERAL PHYSIOLOGY
(2019)
Article
Biophysics
Bharat Ramasubramanian Iyer, Radhakrishnan Mahalakshmi
BIOPHYSICAL JOURNAL
(2019)
Article
Biochemistry & Molecular Biology
Ankit Gupta, Radhakrishnan Mahalakshmi
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Biochemistry & Molecular Biology
Bharat Ramasubramanian Iyer, Swadha Gupta, Henna Noordeen, Roshika Ravi, Meera Daulatrao Pawar, Anjana George, Radhakrishnan Mahalakshmi
Article
Biochemistry & Molecular Biology
Ankit Gupta, Radhakrishnan Mahalakshmi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Shashank Ranjan Srivastava, Radhakrishnan Mahalakshmi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Review
Biochemistry & Molecular Biology
Altmash Khan, Gifty Kuriachan, Radhakrishnan Mahalakshmi
Summary: VDACs play various regulatory roles in cells, including controlling cellular physiology and apoptosis, and directly regulating cancer and neurodegenerative diseases. They achieve these functions by establishing isoform-dependent stereospecific interactomes with cytosolic constituents, ER complexes, and mitochondrial machinery. Misregulation of VDACs can directly lead to mitochondrial dysfunction and their interaction with aggregation-prone proteins may be associated with Alzheimer's and Parkinson's diseases.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Muralikrishna Lella, Radhakrishnan Mahalakshmi
Summary: In this study, a hyperstable stapled beta-hairpin with a defined metal-binding cleft was designed based on the coordination chemistry of metal-binding proteins. The water-soluble peptide showed broad metal-binding properties, with Cu2+ specificity. The importance of the Cys-His tetrad in metal ion selectivity was confirmed through Asp/Glu substitutions.
Article
Chemistry, Multidisciplinary
Anjana George, Roshika Ravi, Pankaj Bharat Tiwari, Shashank Ranjan Srivastava, Vikas Jain, Radhakrishnan Mahalakshmi
Summary: Researchers have identified the structural elements of the host invasion protein Ail in Yersinia pestis and discovered a more stable variant called Out14. They also investigated the molecular mechanism behind the enhanced stability of Out14. These findings have implications for drug screening and medical countermeasures against Yersinia.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Biochemistry & Molecular Biology
Ulfat Mohd Hanif Sayyed, Radhakrishnan Mahalakshmi
Summary: The article discusses the unique properties of the human mitochondrial outer membrane and the importance of the TOM complex. It highlights the recent research progress and the potential impact on alleviating human diseases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Editorial Material
Physiology
Vito De Pinto, Radhakrishnan Mahalakshmi, Angela Messina
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jinam Ravindra Bora, Radhakrishnan Mahalakshmi
Summary: Researchers have successfully used photo-actively modified natural amino acids to accurately study the dynamics, interaction networks, and turnover of cytosolic proteins. They have incorporated 7-fluoro-indole into the human mitochondrial outer membrane protein VDAC2 to generate Trp-Phe/Tyr cross-links. By measuring the kinetics of photo-activated cross-linking with a library of VDAC2 variants, they have discovered a kinetically retarded, tryptophan-independent, and site-specific formation of an unusual fluorophore.
Review
Biochemistry & Molecular Biology
Jinam Ravindra Bora, Radhakrishnan Mahalakshmi
Summary: Diversity in proteins, the biochemical workhorses of cells, is achieved through permutations of the 20 canonical L-amino acids. In addition, proteins can undergo unique non-disulfide cross-links as post-translational modifications, which provide structural stability and unique functional characteristics. This review focuses on a class of amino acid cross-links involving aromatic and sulfur-containing side chains, which not only enhance biochemical characteristics but also have potential as novel chromophores. Further discovery of canonical cross-links will drive the development of protein-specific hyperstable nanostructures, superfoods, and biotherapeutics.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Philipp Grad, Katarina Edwards, Lars Gedda, Victor Agmo Hernandez
Summary: This study investigates the effects of polyethylene glycol-(PEG) modified lipids and gangliosides on the Ca2+ induced interaction between liposomes composed of palmitoyl-oleoyl phosphatidylethanolamine (POPE) and palmitoyl-oleoyl phosphatidylserine (POPS) at physiological ionic strength. The results show that naked liposomes tend to adhere, rupture, and collapse on each other's surfaces upon addition of Ca2+, eventually resulting in the formation of large multilamellar aggregates and bilayer sheets. However, the presence of gangliosides or PEGylated lipids leads to the formation of small, long-lived bilayer fragments/disks. PEGylated lipids seem to be more effective than gangliosides at stabilizing these structures. The study suggests that direct liposome-liposome fusion is not the dominating process triggered by Ca2+ in the systems studied.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Saurabh Saraswat, Archana Chugh
Summary: Cell penetrating peptides (CPP) are important tools for intracellular delivery of molecules. In this study, a novel marine-derived CPP from Engraulis japonicus, called Engraulisin, was reported. Engraulisin demonstrated successful cellular uptake and selective antimicrobial activity against Methicillin-resistant Staphylococcus aureus (MRSA), making it a potential candidate for drug delivery.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Emanuela Efodili, Ashlynn Knight, Maryem Mirza, Cedric Briones, Il-Hyung Lee
Summary: This study demonstrates the spontaneous transfer of small membrane-bound peptides between a supported lipid bilayer and giant unilamellar vesicles in vitro. The transfer occurs through the formation of hemi-fusion stalks and is limited to small peptides due to the highly curved structure of the stalk. This system provides a synthetic platform for studying peptide trafficking between synthetic membranes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Yueqi Niu, Si Jia Chen, Jeffery B. Klauda
Summary: Macrophage membranes in the activated state are more tightly packed, exhibit increased chain order across lipid species, and form specific lipid clusters. These findings provide physiologically accurate models for future computational studies of macrophage membranes and their proteins.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Niki Baccile, Vincent Chaleix, Ingo Hoffmann
Summary: This study measured the bending rigidity of self-assembled structures formed by a new biobased glucolipid bioamphiphile using neutron spin-echo (NSE) technology. The results showed that the bending rigidity of these structures is lower or higher compared to phospholipid membranes, providing a new theoretical basis for the application of these new molecular systems.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Alain Bolano Alvares, Pablo E. A. Rodriguez, Gerardo D. Fidelio
Summary: The behavior of amphiphilic molecules at the air/water interface was studied to evaluate the arrangement formed in a confined area. The surface properties of zwitterionic DPPC lipid and A beta(1-40) amyloid peptide in mixed films were investigated at different temperatures. DPPC undergoes a phase transition depending on temperature and lateral pressure, which allows for the study of its influence on amyloid structure formation.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Lukasz Plachta, Marzena Mach, Magdalena Kowalska, Pawel Wydro
Summary: Resveratrol, a popular phytoalexin found in grapes and red wine, has beneficial effects on the cardiovascular system, exhibits antiviral, antibacterial, and antifungal properties, and may have therapeutic effects against cancer. This study investigates the interaction of resveratrol with model cell membranes, demonstrating changes in their physicochemical parameters and highlighting the role of cholesterol content in resveratrol incorporation. The findings suggest that the molecular mechanism of action of resveratrol may involve interactions with lipid rafts.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Edurne Rujas, Beatriz Apellaniz, Johana Torralba, David Andreu, Jose M. M. Caaveiro, Shixia Wang, Shan Lu, Jose L. Nieva
Summary: This study investigates the role of fusion peptide and Trp-rich membrane proximal external region in HIV-1 fusion and demonstrates that liposome-based formulations containing FP-MPER hybrid peptides can induce the production of specific neutralizing antibodies in rabbits. The results support the use of liposomes as vaccine carriers and the inclusion of lipid membranes in immunogens to elicit specific humoral responses.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Dailin Li, Dingyuan Shi, Lei Wang
Summary: G protein-gated inwardly rectifying potassium (GIRK) channels play a significant role in regulating cell excitability. This study investigated the ion permeation mechanism in GIRK2 mutants using molecular dynamic simulations and QM/MM methods. The results revealed the importance of a multi-ion distribution for ion conduction.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Max J. den Uijl, Arnold J. M. Driessen
Summary: Membrane protein insertion into and translocation across the bacterial cytoplasmic membrane are essential processes facilitated by the Sec translocon. The phospholipid dependence of membrane protein insertion has remained mostly unknown. This study reveals that the insertion of the mannitol permease MtlA into the membrane depends on the presence of phosphatidylglycerol and is stimulated by phosphatidylethanolamine.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Patrick Allen, Adam C. Smith, Vernon Benedicto, Abbas Abdulhasan, Vasanthy Narayanaswami, Enrico Tapavicza
Summary: We explore the stability, size, and structure of nanodiscs formed by the N-terminal domain of apolipoprotein E3 and a variable number of 1,2-dimyristoyl-sn-glycero-3-phosphocholine molecules. Our simulations suggest that nanodiscs containing 240 to 420 DMPC molecules are stable. The antiparallel configuration shows more protein-protein interactions and ionic contacts, as well as greater stability and rigidity compared to the parallel configuration.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Patrick M. Keating, Nicholas P. Schifano, Xinrui Wei, Matthew Y. Kong, Jinwoo Lee
Summary: Lassa virus (LASV) infection is dependent on the fusion of its viral membrane with the host cell membrane, and our study reveals that this fusion process involves pH-dependent conformational changes in the transmembrane domain of LASV. These findings provide valuable insights into the fusion mechanism of LASV and can be utilized in the design of therapeutics to combat Lassa virus infections and prevent its potential spread.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Ashley L. Bennett, Kristen N. Cranford, Austin L. Bates, Christopher R. Sabatini, Hee-Seung Lee
Summary: This study employed molecular dynamics simulations to elucidate the binding, folding, and insertion details of TP10W in the cell membrane. The simulations revealed that TP10W can translocate across the lipid membrane as a monomer, and the charged amino acid side chains can move between lipid leaflets. Comparison with point mutated variants demonstrated significant conformational changes due to charge distribution.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Jessica H. van Wonderen, Jason C. Crack, Marcus J. Edwards, Thomas A. Clarke, Gerhard Saalbach, Carlo Martins, Julea N. Butt
Summary: Electrogenic bacteria transfer excess respiratory electrons to metal oxide particles and electrodes through the MtrCAB complex. The crystal structure of MtrCAB from S. baltica OS185 was resolved, and liquid chromatography mass spectrometry was used to determine the mass values of the three proteins in purified MtrCAB complexes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Review
Biochemistry & Molecular Biology
Yi-Ming Chen, Ching-Tai Lu, Chia-Wen Wang, Wolfgang B. Fischer
Summary: A series of dye ligands were ranked based on docking experiments, selecting the most suitable ligands for binding with different proteins. Additionally, a comparison study was conducted on a series of repurposing drugs and known antivirals.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)