Article
Biochemistry & Molecular Biology
Tamas Lazar, Elizabeth Martinez-Perez, Federica Quaglia, Andras Hatos, Lucia B. Chemes, Javier A. Iserte, Nicolas A. Mendez, Nicolas A. Garrone, Tadeo E. Saldano, Julia Marchetti, Ana Julia Velez Rueda, Pau Bernado, Martin Blackledge, Tiago N. Cordeiro, Eric Fagerberg, Julie D. Forman-Kay, Maria S. Fornasari, Toby J. Gibson, Gregory-Neal W. Gomes, Claudiu C. Gradinaru, Teresa Head-Gordon, Malene Ringkjobing Jensen, Edward A. Lemke, Sonia Longhi, Cristina Marino-Buslje, Giovanni Minervini, Tanja Mittag, Alexander Miguel Monzon, Rohit Pappu, Gustavo Parisi, Sylvie Ricard-Blum, Kiersten M. Ruff, Edoardo Salladini, Marie Skepo, Dmitri Svergun, Sylvain D. Vallet, Mihaly Varadi, Peter Tompa, Silvio C. E. Tosatto, Damiano Piovesan
Summary: The Protein Ensemble Database (PED) has been significantly updated to version 4.0, with cutting-edge technology and an increased amount of data. The database now includes a renewed graphical interface, interactive feature viewer, and high-quality data guaranteed by a new submission process. Additionally, a new search engine allows users to build advanced queries and search all entry fields.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Helena O. Rasmussen, Amit Kumar, Ben Shin, Fisentzos Stylianou, Lee Sewell, Yingqi Xu, Daniel E. Otzen, Jan Skov Pedersen, Steve J. Matthews
Summary: Bacterial functional amyloids contribute to biofilm development and serve as a protective mechanism against the immune system and antibiotics. Recent interest has focused on strategies to target amyloid formation and interrupt biofilm formation due to their antimicrobial potential. The interaction between the components FapA, FapB, and FapC is crucial for Fap fibril biogenesis, with FapA acting as a chaperone to prevent FapC fibrillation in the periplasm.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Evgeniya Tikhonova, Sofia Mariasina, Olga Arkova, Oksana Maksimenko, Pavel Georgiev, Artem Bonchuk
Summary: CLAMP is an essential zinc-finger transcription factor in Drosophila melanogaster and acts as an architectural protein. Its N-terminal region has been found to form homodimers, except in Hymenopterans. Despite lacking secondary structure, this dimerization domain is crucial for CLAMP's in vivo functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Fernando T. Tanouye, Jozismar R. Alves, Francesco Spinozzi, Rosangela Itri
Summary: In this study, protein interactions were investigated using in-solution small angle X-Ray scattering (SAXS) experiments and Monte Carlo (MC) simulations under different conditions. The analysis of experimental data using the HSDY/RPA model combined with MC simulations showed limitations in describing the protein-protein pair potential for highly concentrated systems at low ionic strength. SAXS/MC results revealed that lysozyme concentrations between 2 and 20 mg/mL exhibited similar protein-protein pair potentials, with a surface net charge of around 7 e, protein diameter of 28 Å, attractive well potential decay range of 3 Å, and a depth varying from 1 to 5 kBT depending on temperature and salt addition. Additionally, a novel method combining SAXS with MC simulations was proposed to overcome the limitations of closure relationships in analyzing interacting protein SAXS data.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biophysics
Francesco Pesce, Estella A. Newcombe, Pernille Seiffert, Emil E. Tranchant, Johan G. Olsen, Christy R. Grace, Birthe B. Kragelund, Kresten Lindorff-Larsen
Summary: Diffusion measurements by pulsed-field gradient NMR and fluorescence correlation spectroscopy can be used to probe the hydrodynamic radius of proteins. To tackle the accuracy uncertainty issue in computing the hydrodynamic radius from atomic coordinates, conformational ensembles of intrinsically disordered proteins were built and compared with measurements of compaction. The Kirkwood-Riseman equation was found to provide the best description of the hydrodynamic radius probed by pulsed-field gradient NMR ex-periments.
BIOPHYSICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Lucile Senicourt, Albane le Maire, Frederic Allemand, JoAo E. Carvalho, Laura Guee, Pierre Germain, Michael Schubert, Pau Bernado, William Bourguet, Nathalie Sibille
Summary: Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) form heterodimers to activate target gene transcription by recruiting co-activator complexes. The nuclear receptor co-activator TIF2 interacts with the ligand-binding domain of NRs to mediate recruitment, showing a largely disordered protein with partially structured regions, including the NR-boxes and their evolutionary conserved flanking regions. NMR and X-ray crystallographic data reveal a multisite binding of the NR-boxes and an active role of their flanking regions in the interaction.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Daisuke Tashiro, Shunji Suetaka, Nao Sato, Koji Ooka, Tomoko Kunihara, Hisashi Kudo, Junichi Inatomi, Yuuki Hayashi, Munehito Arai
Summary: Human epidermal growth factor receptors (HER/ERBB) play a vital role in cell proliferation and cancer, but overexpression can cause cancer. Herstatin, an alternative splice variant of HER2, has been identified as a tumor suppressor. This study reveals that a specific domain of herstatin, called Int8, is intrinsically disordered but has a residual helical structure. The research also suggests that a mutant form of Int8, R371I, that is defective in binding to HER2, may lead to the loss of its tumor-suppressive activity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
F. Emil Thomasen, Kresten Lindorff-Larsen
Summary: This review discusses current approaches to determining conformational ensembles of intrinsically disordered proteins (IDPs) and multidomain proteins, including the integration of biophysical experiments and computational models. It also provides examples of recent applications and suggests future directions for research in the field.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Belen Chaves-Arquero, Santiago Martinez-Lumbreras, Nathalie Sibille, Sergio Camero, Pau Bernado, M. Angeles Jimenez, Silvia Zorrilla, Jose Manuel Perez-Canadillas
Summary: This study reveals the functional mechanism of yeast eIF4G1 in translation initiation and stress granules formation using NMR and SAXS techniques. The interactions between eIF4G1 and Pab1, Pub1, and RNA are identified, providing insights into the biological processes involving this key translation initiation factor.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Samuel Naudi-Fabra, Maud Tengo, Malene Ringkjobing Jensen, Martin Blackledge, Sigrid Milles
Summary: Studying the conformational landscape of intrinsically disordered and partially folded proteins is challenging and requires an integrated approach using multiple techniques to accurately describe the conformational ensembles of these proteins. This integrated approach has been successfully tested and validated, providing new insights into the conformational landscape of viral proteins and demonstrating its potential for integrative dynamic structural biology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Physical
Abigail Barclay, Birthe B. Kragelund, Lise Arleth, Martin Cramer Pedersen
Summary: Recent advances in protein expression protocols have allowed for the investigation of structurally complex and disordered biomolecules using small-angle scattering experiments. A modeling scheme has been developed that combines classical form factor based modeling with spherical harmonics-based formulation to accurately calculate scattering profiles from these complex samples. The scheme can account for flexible domains and other structurally elaborate components, and we demonstrate its utility through a case study on a growth hormone receptor membrane protein. We also explore how the scattering profiles vary under different contrasts and discuss the implications for data modeling.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2023)
Review
Chemistry, Analytical
Seema Thakral, Kyungtae Kim
Summary: Small-angle scattering (SAS) is a versatile analytical technique that provides detailed structural information at the nanometer scale. It has diverse applications in pharmaceutical material characterization, including identification of liquid-crystalline mesophase of drugs, study of excipient microstructure influence, and optimization of solid dispersions and protein-based therapeutics formulations.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Souvik Mondal, Krishna Prasad Ghanta, Sanjoy Bandyopadhyay
Summary: This study investigates the dynamic properties of water near the α-synuclein protein associated with Parkinson's disease. The results show that the translational and rotational mobility of water molecules near the peptide segments are significantly restricted, with water near the hydrophobic segment exhibiting more restricted diffusivity. The time scales of peptide-water and water-water hydrogen bond relaxations correlate with the diffusion of interfacial water molecules. The hindered dynamic environment near a specific segment can enhance early stages of peptide aggregation.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Multidisciplinary Sciences
J. S. Park, J. D. Almer, K. C. James, L. J. Natanson, S. R. Stock
Summary: Members of subclass Elasmobranchii possess bioapatite mineralization in their cartilage skeletons, which has similar crystallography to bone but exhibits some differences. The mineral phase in shark centra has larger nanocrystallite sizes and is associated with less microstrain compared to bone.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2022)
Article
Chemistry, Physical
Souvik Dey, Matthew MacAinsh, Huan-Xiang Zhou
Summary: For intrinsically disordered proteins (IDPs), the dynamics of the backbone play a key role in encoding their function. The dynamics are regulated by local interactions, secondary structures, and glycines. These sequence-dependent changes in backbone dynamics allow IDPs to respond to binding partners in a versatile manner.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Neurosciences
Tee Jong Huat, Tessa Onraet, Judith Camats-Perna, Estella A. Newcombe, Kim C. Ngo, Ashley N. Sue, Mehdi Mirzaei, Frank M. LaFerla, Rodrigo Medeiros
Summary: This study reveals that MyD88 plays a pivotal role in the regulation of astrocyte response to Alzheimer's disease (AD), with upregulated expression in AD patients. Deletion of astrocytic MyD88 protects mice from acute synaptic toxicity and cognitive impairment caused by beta-amyloid. Loss of astrocytic MyD88 results in altered astrocyte reactivity, lower levels of immune-related proteins, and higher expression of synaptic-related proteins in response to beta-amyloid.
Article
Biochemistry & Molecular Biology
Amanda B. Abildgaard, Vasileios Voutsinos, Soren D. Petersen, Fia B. Larsen, Caroline Kampmeyer, Kristoffer E. Johansson, Amelie Stein, Tommer Ravid, Claes Andreasson, Michael K. Jensen, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and chaperone-binding regions may function as PQC degrons. A canonical Hsp70-binding motif, the APPY peptide, functions as a dose-dependent PQC degron in yeast and human cells. The number of exposed Hsp70-binding sites in the yeast proteome correlates with reduced protein abundance and half-life.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Kristoffer E. Johansson, Bayan Mashahreh, Rasmus Hartmann-Petersen, Tommer Ravid, Kresten Lindorff-Larsen
Summary: Effective proteome homeostasis is crucial for cell and organism survival. Cells have efficient quality control systems to monitor and remove misfolded proteins. The nature and sequence properties of quality-control degrons are still unknown.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Audrone Valanciute, Lasse Nygaard, Henrike Zschach, Michael Maglegaard Jepsen, Kresten Lindorff-Larsen, Amelie Stein
Summary: Calculating changes in protein stability (AAG) is important for predicting the consequences of amino acid substitutions in protein engineering and interpreting genomic variants for disease risk. This study investigates the accuracy of AAG values predicted on homology models compared to crystal structures, and finds that they are equally accurate as long as the sequence identity of the model template to the target protein is at least 40%. The results show that stability calculations performed on homology models can substitute for those on crystal structures with acceptable accuracy.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Fia B. Larsen, Matteo Cagiada, Jonas Dideriksen, Amelie Stein, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: Catechol-O-methyltransferase (COMT) is an important enzyme involved in the metabolism of neurotransmitters and catecholamine drugs, and its variation can affect pharmacokinetics and drug availability.
Review
Biotechnology & Applied Microbiology
Yixin Rong, Sheila Ingemann Jensen, Kresten Lindorff-Larsen, Alex Toftgaard Nielsen
Summary: The expression of correctly folded and functional heterologous proteins is crucial in biotechnological production processes. Bacterial platform organisms like E. coli are commonly used due to their proven suitability at an industrial scale, but can suffer from protein aggregation and low functional protein levels. This review explores cellular mechanisms influencing protein folding and expression across different organisms, and discusses experimental methods to improve protein folding, such as codon optimization and chaperone co-production.
BIOTECHNOLOGY ADVANCES
(2023)
Letter
Biochemistry & Molecular Biology
Kaare Teilum, Johan G. Olsen, Birthe B. Kragelund
Article
Biochemistry & Molecular Biology
Yulian Gavrilov, Andreas Prestel, Kresten Lindorff-Larsen, Kaare Teilum
Summary: Slow conformational changes are important for protein function, but their impact on the overall folding stability is not well understood. This study investigates the effects of L49I and I57V substitutions on the slow conformational dynamics of CI2. The results show that these substitutions have minimal impact on the structure of the excited state, but the stability of the excited state is influenced by the stability of the main state. The interactions between substituted residues and water molecules play a role in linking subtle structural changes to slow conformational changes in the protein.
Article
Biology
F. Emil Thomasen, Matthew J. Cuneo, Tanja Mittag, Kresten Lindorff-Larsen
Summary: Speckle-type POZ protein (SPOP) is a key protein in the ubiquitin proteasome system, with important roles in cell-cycle control, development, and cancer pathogenesis. This study combines small-angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations to characterize the conformational ensembles and oligomeric states of SPOP. The results suggest that SPOP oligomers behave as rigid, helical structures with flexible substrate-binding domains.
Article
Biochemistry & Molecular Biology
Antoni Kowalski, Cristine Betzer, Sigrid Thirup Larsen, Emil Gregersen, Estella A. Newcombe, Montana Caballero Bermejo, Viktor Wisniewski Bendtsen, Jorin Diemer, Christina Ernstsen, Shweta Jain, Alicia Espina Bou, Annette Eva Langkilde, Lene N. Nejsum, Edda Klipp, Robert Edwards, Birthe B. Kragelund, Poul Henning Jensen, Poul Nissen
Summary: This study shows that monomeric alpha-synuclein can activate plasma membrane Ca2+-ATPase (PMCA) to promote calcium clearance in neurons. The colocalization of alpha-synuclein and PMCA at neuronal synapses suggests a potential physiological function for alpha-synuclein in regulating calcium expulsion.
Article
Chemistry, Medicinal
Jie Zang, Felix Peters, Yves Cambet, Eugenia Cifuentes-Pagano, Munira Mohamed Shishay Hissabu, Christopher M. Dustin, Lars Henrik Svensson, Martin Mariboe Olesen, Mathias Feldt Lomholt Poulsen, Stig Jacobsen, Pernille Sonderby Tuelung, Dilip Narayanan, Annette Eva Langkilde, Michael Gajhede, Patrick J. Pagano, Vincent Jaquet, Frederik Vilhardt, Anders Bach
Summary: In this study, we optimized and explored bivalent small-molecule drugs targeting the NOX2 subunit p47phox and identified compounds with high binding affinities and cellular activities, demonstrating the potential of p47phox as an effective small-molecule target. This has important implications for the research and development of therapeutic drugs for related diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nina L. Jacobsen, Magnus Bloch, Peter S. Millard, Sarah F. Ruidiaz, Jonas D. Elsborg, Wouter Boomsma, Ruth Hendus-Altenburger, Rasmus Hartmann-Petersen, Birthe B. Kragelund
Summary: This study found that Schizosaccharomyces pombe Dss1 is phosphorylated by casein kinase 2 at three threonine sites in its linker region. The phosphorylation does not affect its ubiquitin binding ability, but slightly destabilizes the C-terminal alpha-helix and directly interacts with the forkhead-associated domain of the RING-FHA E3-ubiquitin ligase defective in mitosis 1 (Dma1). These phosphorylation sites are absent in human Dss1.
Correction
Multidisciplinary Sciences
Andrea Sottini, Alessandro Borgia, Madeleine B. Borgia, Katrine Bugge, Daniel Nettels, Aritra Chowdhury, Petur O. Heidarsson, Franziska Zosel, Robert B. Best, Birthe B. Kragelund, Benjamin Schuler
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Altair Brito Dos Santos, Siganya Thaneshwaran, Lara Kamal Ali, Cesar Ramon Romero Leguizamon, Yang Wang, Morten Pilgaard Kristensen, Annette E. Langkilde, Kristi A. Kohlmeier
Summary: This study found that a-syn(M) has different effects on female LDT neurons compared to male. In females, a-syn(M) decreases membrane excitability and reduces intracellular calcium, which depends on inhibitory acid transmission and leads to decreased amplitude and frequency of sEPSCs, as well as reduced action potential firing rate. It was also found that a-syn(M) induces higher neurodegeneration in males compared to females through inhibitory amino acid transmission. GABA receptor agonists were associated with reduced cell death in males.
CELL AND BIOSCIENCE
(2023)
Review
Cell Biology
Alex S. Holehouse, Birthe B. Kragelund
Summary: Intrinsically disordered protein regions, lacking a stable 3D structure, are structurally heterogeneous and widely present in all kingdoms of life. Despite their lack of a defined structure, these regions play essential roles in cellular processes and can be regulated by their structural and chemical context. Recent studies have advanced our understanding of the link between protein sequence and conformational behavior in disordered regions, but the connection between sequence and molecular function is still not well defined.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)