Review
Biochemistry & Molecular Biology
Goro Kato
Summary: This review discusses the structural and functional aspects of Src protein and its regulatory mechanism. By reviewing nuclear magnetic resonance analyses and recent studies, the authors explore new characteristics and regulatory roles of Src protein. Finally, the new regulatory roles are integrated with the canonical model to elucidate the functions of full-length Src.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Guanlan Fan, Fan Wang, Yurou Chen, Qian Zheng, Jie Xiong, Qiongying Lv, Kejia Wu, Jiaqiang Xiong, Lei Wei, Dongqing Li, Jiachen Zhang, Wei Zhang, Feng Li
Summary: In this study, OTUD1 is identified as an Akt-associated protein and is downregulated upon Akt activation. Ectopic OTUD1 inhibits Akt phosphorylation, and a short peptide (OUN-36) located in the OTUD1 N-terminal intrinsically disordered region strongly binds to the Akt PH domain. OUN-36-based therapy efficiently abrogates Akt feedback reactivation and sensitizes cancer cells to chemotherapy and immunotherapy.
Article
Biochemistry & Molecular Biology
Emilie Aponte, Marie Lafitte, Audrey Sirvent, Valerie Simon, Maud Barbery, Elise Fourgous, Mariano Maffei, Florence Armand, Romain Hamelin, Julie Pannequin, Philippe Fort, Miquel Pons, Serge Roche, Yvan Boublik
Summary: This study reveals the important role of the unique domain ULBR in Src tyrosine kinase in malignant cell transformation. The ULBR is involved in membrane anchoring, MAPK signaling, and phosphorylation of specific membrane-localized tyrosine kinases needed for Src oncogenic signaling.
Article
Multidisciplinary Sciences
Jingyao Li, Bojing Jiang, Xinyuan Chang, Han Yu, Yichao Han, Fuzhong Zhang
Summary: The authors have developed a method to enhance the strength of low molecular-weight protein materials by fusing intrinsically-disordered mussel foot protein fragments. This approach can be applied to a wide range of protein-based materials and has the potential to achieve high yields.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Cecilia Chavez-Garcia, Jerome Henin, Mikko Karttunen
Summary: This research characterizes the structure and dynamics of MeCP2 protein and provides a computational model that is compatible with experimental data. The study reveals two main conformations of MeCP2 and compares the model with experimental observations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Multidisciplinary
Valentin Bauer, Boris Schmidtgall, Gergo Gogl, Jozica Dolenc, Judit Osz, Yves Nomine, Camille Kostmann, Alexandra Cousido-Siah, Andre Mitschler, Natacha Rochel, Gilles Trave, Bruno Kieffer, Vladimir Torbeev
Summary: This study utilized a specific amino acid substitution pattern to modify the free activation domain of transcriptional coactivator ACTR, resulting in increased binding affinity to CREB-binding protein. The X-ray structure of the modified ACTR domain - NCBD complex revealed a unique conformation of ACTR, demonstrating a strategy for characterizing individual conformational states of IDPs.
Article
Biochemistry & Molecular Biology
Alexander S. Krois, Sangho Park, Maria A. Martinez-Yamout, H. Jane Dyson, Peter E. Wright
Summary: The structure and interactions of the C-terminal region of p53 protein have been studied. Full-length p53 constructs were generated using trans-intein splicing and isotopically labeled for NMR analysis. This study provides high-resolution insights into the behavior of the C-terminal domains within the full-length protein and the molecular basis of its interactions with DNA.
Article
Chemistry, Inorganic & Nuclear
Maryann Morales, Raheleh Ravanfar, Paul H. Oyala, Harry B. Gray, Jay R. Winkler
Summary: The first encoded protein of SARS-CoV-2, Nsp1, binds to the human 40S ribosome and inhibits the synthesis of host proteins, thereby suppressing the innate immune response. The last 33 residues of the unstructured C-terminus of Nsp1 adopt a specific geometric structure upon binding to the ribosome.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Samuel Wohl, Matthew Jakubowski, Wenwei Zheng
Summary: The study introduced a new model to explain the influence of salt on protein structure, revealing the significant role of salting-out effect in IDP sequences, especially those with moderately charged residues. This model also shows general applicability in conformation studies of other proteins.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Elisia A. Paiz, Jeffre H. Allen, John J. Correia, Nicholas C. Fitzkee, Loren E. Hough, Steven T. Whitten
Summary: The study revealed that disordered proteins with a propensity for phase separation have smaller monomeric sizes and higher beta-turn tendencies. A proposed physical mechanism involving beta-turn structures explains the role of beta-turns in protein phase separation, providing energetically favored nucleation points. The research also introduced a new algorithm, ParSe, for predicting phase-separating protein regions based on primary sequences.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biology
Utsab R. Shrestha, Jeremy C. Smith, Loukas Petridis
Summary: The study demonstrates that enhancing the sampling using Hamiltonian replica exchange molecular simulation (HREMD) leads to accurate unbiased ensembles of intrinsically disordered proteins. Standard molecular simulation cannot reproduce small-angle scattering data as well as HREMD, highlighting the utility of the suggested approach.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Feng Yuan, Christopher T. Lee, Arjun Sangani, Justin R. Houser, Liping Wang, Eileen M. Lafer, Padmini Rangamani, Jeanne C. Stachowiak
Summary: Membrane curvature is crucial for cellular functions and recent studies have revealed the role of intrinsically disordered proteins in driving membrane bending. Repulsive interactions among disordered domains lead to convex curvature, while attractive interactions result in concave curvature, forming membrane-bound liquid-like condensates. This study investigates the effects of disordered domains containing both repulsive and attractive interactions on curvature. The findings show that the position of the attractive or repulsive domain relative to the membrane determines the curvature, with increasing ionic strength altering the transition from convex to concave. These results provide design rules for membrane bending by disordered proteins.
Article
Biochemistry & Molecular Biology
Elek Telek, Kristof Karadi, Jozsef Kardos, Andras Kengyel, Zsuzsanna Fekete, Henriett Halasz, Miklos Nyitrai, Beata Bugyi, Andras Lukacs
Summary: The Myo16Tail protein region plays a crucial role in neuronal functioning, cell cycle regulation, and phosphoinositide 3-kinase signaling. It interacts with the N-terminal ankyrin domain of myosin 16, demonstrating high structural flexibility and intrinsic disorder. These features suggest that Myo16Tail may act as a flexible display site crucial in post-translational modifications and regulatory functions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Jing Zhao, Alan Blayney, Xiaorong Liu, Lauren Gandy, Weihua Jin, Lufeng Yan, Jeung-Hoi Ha, Ashley J. Canning, Michael Connelly, Chao Yang, Xinyue Liu, Yuanyuan Xiao, Michael S. Cosgrove, Sozanne R. Solmaz, Yingkai Zhang, David Ban, Jianhan Chen, Stewart N. Loh, Chunyu Wang
Summary: Epigallocatechin gallate (EGCG) in green tea induces apoptosis in cancerous cells through a direct interaction with the tumor suppressor p53, inhibiting p53 ubiquitination by its regulatory E3 ligase MDM2 and stabilizing p53 for anti-tumor activity.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Sylvie Ricard-Blum, John R. Couchman
Summary: Syndecans are transmembrane heparan sulfate proteoglycans that play potential roles in development and disease, including vascular diseases, inflammation, and various cancers. The recent structural data provides insights into their complex functions, including both intrinsic signaling and cooperative mechanisms with other receptors. The interaction with glycanation and partner proteins impacts the conformation and function of syndecan. Genetic models suggest that syndecans act as mechanosensors and influence actin cytoskeleton organization. The clustering of syndecan with other cell surface receptors has implications in tissue differentiation and disease. The understanding of structure/function relationships in mammalian syndecans is important due to their diagnostic and therapeutic potential in cancer.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Petr Konarev, Melissa A. Graewert, Cy M. Jeffries, Masakazu Fukuda, Taisiia A. Cheremnykh, Vladimir V. Volkov, Dmitri Svergun
Summary: SAXS is commonly used for structural analysis of biological macromolecules in solution, and combining SAXS with chromatography setups has become popular in research. The computer program EFAMIX, based on evolving factor analysis (EFA), efficiently restores scattering and concentration profiles of components from mixed SAXS data, proving useful for interpretation and analysis of fractions in the sample.
Article
Biochemistry & Molecular Biology
Eleonora V. Shtykova, Maxim V. Petoukhov, Andrey A. Mozhaev
Summary: DNA-binding protein from starved cells (Dps) is a dodecamer mini-ferritin that plays a crucial role in protecting the bacterial genome and acting as an iron depot. This study investigated the formation of iron oxide nanoparticles inside the Dps dodecamer and found that the size of the nanoparticles ranged from 2 to 4 nm. The presence of iron ions in the Dps surface layer was also observed, which is important for the protein's protective functions.
BIOCHEMISTRY-MOSCOW
(2022)
Biographical-Item
Chemistry, Multidisciplinary
Dmitri Svergun, Jill Trewhella
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2022)
Article
Multidisciplinary Sciences
Ivan Corbeski, Xiaohu Guo, Bruna Eckhardt, Domenico Fasci, Wouter Wiegant, Melissa A. Graewert, Kees Vreeken, Hans Wienk, Dmitri Svergun, Albert J. R. Heck, Haico van Attikum, Rolf Boelens, Titia K. Sixma, Francesca Mattiroli, Hugo van Ingen
Summary: Nucleosome assembly requires specific histone chaperones, but this study found that the acidic domain of DNA repair factor APLF can directly assemble the histone octamer and deposit it on DNA to form nucleosomes, which may be a mechanism for histone chaperone function at sites where chromatin is temporarily disrupted.
Article
Biochemistry & Molecular Biology
Maxime Killer, Giada Finocchio, Haydyn D. T. Mertens, Dmitri I. Svergun, Els Pardon, Jan Steyaert, Christian Loew
Summary: Proton-coupled Oligopeptide Transporters (POTs) mediate the uptake of short di- and tripeptides. This study determined the structure of DtpC and provided insights into its ligand specificity using cryogenic electron microscopy (cryo-EM). The research highlights the value of nanobodies for structure determination of low molecular weight integral membrane proteins.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Stefan R. Marsden, Hein J. Wijma, Michael K. F. Mohr, Ines Justo, Peter-Leon Hagedoorn, Jesper Laustsen, Cy M. Jeffries, Dmitri Svergun, Luuk Mestrom, Duncan G. G. McMillan, Isabel Bento, Ulf Hanefeld
Summary: This study reveals a novel mechanism of enzyme activity regulation, which involves the dynamic movement of the metal cofactor between two coordination spheres without protein scaffold rearrangements. This type of regulation may be widespread but has been largely overlooked.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Tomasz H. Benedyk, Viv Connor, Eve R. Caroe, Maria Shamin, Dmitri I. Svergun, Janet E. Deane, Cy M. Jeffries, Colin M. Crump, Stephen C. Graham
Summary: Herpes simplex virus-1 (HSV-1) alters cellular membrane lipid composition during infection. This study demonstrates that a virus-encoded protein, pUL21, promotes the conversion of ceramide (Cer) to sphingomyelin (SM) by activating CERT. The study also reveals the importance of specific protein-protein interactions in HSV-1 mediated sphingolipid metabolism.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biophysics
I. S. Vaskan, A. T. Prikhodko, M. V. Petoukhov, E. V. Shtykova, N. V. Bovin, A. B. Tuzikov, V. A. Oleinikov, A. V. Zalygin
Summary: The detailed analysis of the surface structure of nanoparticles is essential for the rational design of drug delivery systems. However, characterizing the surface structure under physiological conditions is challenging. In this study, the combination of SAXS contrast variation and ab initio bead modeling was used to investigate nanoparticle surface structure. By gradually increasing the solvent electron density, the shell coating thickness and uniformity around the nanoparticle core were assessed.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Biochemistry & Molecular Biology
Iain M. Hay, Maria Shamin, Eve R. Caroe, Ahmed S. A. Mohanned, Dmitri I. Svergun, Cy M. Jeffries, Stephen C. Graham, Hayley J. Sharpe, Janet E. Deane
Summary: Type IIB receptor protein tyrosine phosphatases mediate cell adhesion and signaling through their extracellular and cytoplasmic domains, respectively. The crystal structure of PTPRK has revealed an intermembrane adhesion mode consistent with other family members. Comparison with PTPRM structure suggests that conformational differences between the domains may contribute to homophilic specificity. Analysis of the full-length PTPRM and PTPRK proteins using small-angle X-ray scattering reveals rigid extended conformations and one residue difference at the interaction interface that affects dimer formation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Goksin Liu, Erhan Ekmen, Farzaneh Jalalypour, Haydyn D. T. Mertens, Cy M. Jeffries, Dmitri Svergun, Ali Rana Atilgan, Canan Atilgan, Zehra Sayers
Summary: This study combines molecular dynamics (MD) simulations with small angle x-ray scattering (SAXS) measurements to investigate the range of conformations and populations of a pH/ionic strength (IS) sensitive protein. The protein studied is the periplasmic ferric binding protein A (FbpA) involved in iron capture from higher organisms by bacteria. The study reveals the detectable changes in conformational distribution of FbpA under different conditions, but detection of conformational changes due to point mutation D52A and changes in ionic strength has been challenging.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Gabriela Guedez, Gabriele Loers, Cy M. Jeffries, Sandra Kozak, Rob Meijers, Dmitri I. Svergun, Melitta Schachner, Christian Loew
Summary: The cell adhesion molecule L1 plays crucial roles in neural development, regeneration, synaptic plasticity, and tumor cell migration. L1 is a member of the immunoglobulin superfamily and consists of Ig-like domains and fibronectin type III homologous repeats. The second Ig-like domain is involved in cell binding, and the fibronectin type III homologous repeats contribute to signal transduction.
Article
Biochemical Research Methods
Masakazu Fukuda, Melissa A. Graewert, Cy M. Jeffries, Dmitri I. Svergun, Tadao Yamazaki, Akiko Koga, Yuji Yamanaka
Summary: This study investigates the acidic variants of therapeutic monoclonal antibodies (mAbs) using a refolding approach. The results showed that these acidic variants are conformational variants with minor and localized conformational changes.
ANALYTICAL BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Stefano Da Vela, Giovanni Saudino, Francesca Lucarelli, Lucia Banci, Dmitri I. Svergun, Simone Ciofi-Baffoni
Summary: In humans, the biosynthesis and trafficking of mitochondrial [4Fe-4S]2+ clusters is a highly coordinated process that requires a complex protein machinery. Two [2Fe-2S]2+ clusters are converted into a [4Fe-4S]2+ cluster on an ISCA1-ISCA2 complex. NFU1 is the accessory protein that first receives the [4Fe-4S]2+ cluster from the ISCA1-ISCA2 complex.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Oncology
Negar Khazan, Emily R. R. Quarato, Niloy A. A. Singh, Cameron W. A. Snyder, Taylor Moore, John P. P. Miller, Masato Yasui, Yuki Teramoto, Takuro Goto, Sabeeha Reshi, Jennifer Hong, Naixin Zhang, Diya Pandey, Priyanka Srivastava, Alexandra Morell, Hiroki Kawano, Yuko Kawano, Thomas Conley, Deepak M. M. Sahasrabudhe, Naohiro Yano, Hiroshi Miyamoto, Omar Aljitawi, Jane Liesveld, Michael W. W. Becker, Laura M. M. Calvi, Alexander S. S. Zhovmer, Erdem D. D. Tabdanov, Nikolay V. V. Dokholyan, David C. C. Linehan, Jeanne N. N. Hansen, Scott A. A. Gerber, Ashoke Sharon, Manoj K. K. Khera, Peter W. W. Jurutka, Natacha Rochel, Kyu Kwang Kim, Rachael B. B. Rowswell-Turner, Rakesh K. K. Singh, Richard G. G. Moore
Summary: The study identifies vitamin D/VDR as the driver of PD-L1 expression in AML and other cancers. They have developed a small molecule inhibitor called MeTC7 to target PD-L1 and inhibit tumorigenesis driven by PD-L1/PD-1. This provides a potential alternative to antibodies for controlling immune evasion in tumors.
Article
Biochemistry & Molecular Biology
Alexander L. L. Ksenofontov, Maxim V. V. Petoukhov, Vladimir V. V. Matveev, Natalia V. V. Fedorova, Pavel I. I. Semenyuk, Alexander M. M. Arutyunyan, Tatiana I. I. Manukhova, Ekaterina A. A. Evtushenko, Nikolai A. A. Nikitin, Olga K. V. Karpova, Eleonora V. V. Shtykova
Summary: The amino acid sequences of the coat proteins (CPs) of PVX and AltMV share about 40% identity. The N-terminal domains of these proteins differ in sequence and the presence of an N-terminal fragment in PVX CP. The N-terminal domain of PVX CP contributes to the higher thermal stability and ordered structure of PVX virions compared to AltMV.
BIOCHEMISTRY-MOSCOW
(2023)