Article
Biology
Gulcin Vardar, Andrea Salazar-Lazaro, Marisa Brockmann, Marion Weber-Boyvat, Sina Zobel, Victor Wumbor-Apin Kumbol, Thorsten Trimbuch, Christian Rosenmund
Summary: Studies show that in synaptic transmission, STX1's H-abc domain is essential while the N-peptide is dispensable. The N-peptide in STX1A plays a regulatory role in synaptic release, and the open conformation of STX1 governs vesicle fusogenicity. neurotransmitter release can still proceed even when the interaction modes between STX1A and Munc18-1 are interrupted, requiring a revision of the conceptualization of their interaction.
Article
Biochemistry & Molecular Biology
Xiaolei Chen, Zhongmei Yang, Wenfeng Wang, Kaiyue Qian, Mingjie Liu, Junchao Wang, Mingzhu Wang
Summary: This study elucidated the binding mechanisms of RBM45's N-terminal tandem RRM domains with DNA, including specific RNA/ssDNA sequences and critical residues. These findings help to uncover the physiological functions and pathological significance of RBM45.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Rajavenkatesh Krishnamoorthy, Meenakshi Singh, Parthiban Anaikutti, L. Edwin Paul, Sivasankaran Dhanasekaran, Thennarsu Sathiah
Summary: Two novel short peptides, P1 and P2, were designed and synthesized, which showed strong binding ability to receptors and proteins related to tumor. The peptides demonstrated good anticancer activities against cancer cells and low cytotoxicity to normal cells. In silico studies were conducted to predict the binding sites and orientation of the peptides for potential anticancer targets.
BIOORGANIC CHEMISTRY
(2023)
Article
Biology
Melanie Berbon, Denis Martinez, Estelle Morvan, Axelle Grelard, Brice Kauffmann, Jehan Waeytens, Frank Wien, Veronique Arluison, Birgit Habenstein
Summary: Hfq is a pleitropic actor that plays important roles in stress response and virulence in bacterial cells. It assembles into hexameric structures and has an intrinsically disordered C-terminal region. Our study reveals that an 11-residue motif at the C-terminal end of Hfq can form amyloid-like filaments. This suggests that Hfq may exist in two forms in cells, either as soluble hexamers or as self-assembled hexamers through amyloid-reminiscent interactions.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yi-Kai Chen, Isabella A. Simon, Ivan Maslov, Ivan E. Oyarce-Pino, Ketav Kulkarni, Denham Hopper, Marie-Isabel Aguilar, Naveen Vankadari, Brad R. S. Broughton, Mark P. Del Borgo
Summary: By replacing the N-acyl cap, the self-assembly structure of β-peptides can be switched from fibrillar to spherical structures. The Fmoc-protected β-3 peptides can form stable and cargo-encapsulating spherical particles, which can efficiently deliver cargo to cells.
Article
Multidisciplinary Sciences
Kyungmin Kim, Thomas W. Kirby, Lalith Perera, Robert E. London
Summary: The study investigated the phosphopeptide binding characteristics of Nbs1 BRCT1/2 and identified structural homology with TopBP1 BRCT7/8 through molecular modeling. These features provide insight into the basis for interaction of SDT motifs with the BRCT1/2 domains and allowed identification of high and low affinity ligands.
SCIENTIFIC REPORTS
(2021)
Article
Food Science & Technology
Benwei Zhu, Yinxiao Xu, Hui Wang, Zhong Yao
Summary: A new chitosanase, CscC, was cloned and expressed, and its enzymatic properties were improved by truncating a structural domain. Two mutants, CscC-CT1 and CscC-CT2, were obtained, with CscC-CT1 showing higher specific activity and better thermal and metal ion stability. This chitosanase provides an efficient enzyme tool for the clean production of chitosan oligosaccharides.
Article
Biology
Mark Ultsch, Michael J. Holliday, Stefan Gerhardy, Paul Moran, Suzie J. Scales, Nidhi Gupta, Francesca Oltrabella, Cecilia Chiu, Wayne Fairbrother, Charles Eigenbrot, Daniel Kirchhofer
Summary: The study presents X-ray and NMR structures of the N-terminal domain of closely related innate immunity proteins ApoL1 and ApoL2, revealing differences between them and shedding light on the related functions within the small ApoL family. It also highlights the conformational flexibility and unique features of ApoL1's long helix 5, suggesting a Bcl-2-independent role in cytotoxicity. These findings should facilitate a more comprehensive understanding of the structure and function of the ApoL immune protein family.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Ran He, Guanhao Chen, Zhiwei Li, Jianchao Li
Summary: In this study, it was found that the N-terminal coil structure of Rpgrip1l is made up of two parallel dimers. Overexpression of these dimers significantly shortened the length of primary cilia, and this effect was dependent on the formation of dimers. It was also observed that the N-terminal structure of Rpgrip1 in mouse and human differed significantly from Rpgrip1l. Furthermore, disease-related mutations were found to alter the dimeric states of Rpgrip1l or Rpgrip1, possibly explaining the mechanisms behind the associated pathologies.
Article
Biotechnology & Applied Microbiology
Masayoshi Sakaguchi, Hinako Mukaeda, Anna Kume, Yukiko Toyoda, Takumi Sakoh, Masao Kawakita
Summary: The N-terminal region of Thermoplasma trehalase Tvn1315 plays a critical role in protein solubility, with specific residues affecting the solubilization process. Mutations at the 9th position of Tvn1315 revealed that aromatic and bulky hydrophobic residues can function properly, while residues with hydroxy groups impair solubility. The results suggest that the solubility of the catalytic domain depends on the folding of the beta-sandwich domain.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Chemistry, Medicinal
Youchao Deng, Sunbin Deng, Yi-Hsun Ho, Sarah M. Gardner, Zhi Huang, Ronen Marmorstein, Rong Huang
Summary: The study designed and prepared a series of highly potent NatD bisubstrate inhibitors, showing high specificity towards NatD and strong competitive characteristics, providing a rational path for future inhibitor development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Leena Aggarwal, Parbati Biswas
Summary: The hydration thermodynamics of Aβ and its FAD mutants were investigated using MD simulations and 3D-RISM theory, revealing that mutations affect hydration free energy through electrostatic and nonelectrostatic contributions, resulting in different aggregation propensities and early onset Alzheimer's disease risk.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Eunhye Lee, Chanshin Kang, Pasi Purhonen, Hans Hebert, Karim Bouazoune, Sungchul Hohng, Ji-Joon Song
Summary: CHD7 is a crucial chromatin remodeler, and its N-CRD region is essential for its ATPase stimulation and nucleosome remodeling activity. Mutations in this region can lead to defects in CHD7 function, affecting remodeling activity.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jing-Ming Shi, Hai-Yun Li, Hang Liu, Li Zhu, Yi-Bo Guo, Jie Pei, Hao An, Yan-Song Li, Sha-Di Li, Ze-Yu Zhang, Yi Zheng
Summary: Alzheimer's disease is associated with distinct amyloid-beta peptide (Aβ) assemblies, and the aggregation and neurotoxicity of Aβ depend on the N-terminal amino acid residues. The study found that N-terminal mutational peptides of Aβ42, including Aβ42(R5G), Aβ42(Y10F), and rat Aβ42, formed diffusible ligand, protofibrils, and fibrils that were indistinguishable by conventional techniques. However, the amyloid fibrillation was greatly inhibited in vitro. The results suggest that the N-terminus of Aβ is important for its fibrillation and neurotoxicity.
Article
Biochemistry & Molecular Biology
Jui-Hung Weng, Chiara R. Trilling, Pallavi Kaila Sharma, Eliza Stoermer, Jian Wu, Friedrich W. Herberg, Susan S. Taylor
Summary: Mutations in the LRRK2 gene increase the risk of Parkinson's disease. LRRK2 is a protein kinase with seven well-folded domains. The LRR-ROC linker becomes disordered when LRRK2 is activated, and a key residue W1295 blocks substrate access. High-dynamics simulations show the stability of the LRR-Linker motif, P + 1 loop, and inhibitory helix.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biology
Oliver W. Bayfield, Alasdair C. Steven, Alfred A. Antson
Article
Biochemistry & Molecular Biology
Kristina V. Tugaeva, James Titterington, Dmitriy V. Sotnikov, Eugene G. Maksimov, Alfred A. Antson, Nikolai N. Sluchanko
Article
Multidisciplinary Sciences
Sze Lei Pang, Sri Anusha Matta, Yang Yie Sio, Yu Ting Ng, Yee-How Say, Chyan Leong Ng, Fook Tim Chew
Summary: The study identified K44 and E46 residues as major IgE-binding residues of the Der p 23 allergen for HDM-sensitized individuals. Individuals sensitized only to HDM have a higher number of IgE-binding residues compared to polysensitized individuals. Those with allergic multimorbidity and moderate-to-severe allergic rhinitis also exhibit a higher number of IgE-binding residues.
SCIENTIFIC REPORTS
(2021)
Article
Biotechnology & Applied Microbiology
Susanne Nieland, Susann Barig, Julian Salzmann, Frauke Gehrau, Arief Izzairy Zamani, Annabell Richter, Julia Ibrahim, Yvonne Graeser, Chyan Leong Ng, Klaus-Peter Stahmann
Summary: By comparing different fungi, it was found that Aspergillus fumigatus AR04 had a faster hyphal growth rate at higher temperatures, and could even grow at 49 degrees Celsius. The fungus reached a steady state at a higher dilution rate of 0.7 h(-1) at 40 degrees Celsius compared to other fungi.
MICROBIAL BIOTECHNOLOGY
(2021)
Article
Chemistry, Physical
Mengyu Ge, Robert W. Molt, Huw T. Jenkins, G. Michael Blackburn, Yi Jin, Alfred A. Antson
Summary: The octahedral TSA complex MgF3(H2O)(-) observed in a 1.5 A resolution crystal structure of Zika virus NS3 helicase, along with independent validation by F-19 NMR, highlights the significance of this complex in studies of biological motors.
Article
Biochemistry & Molecular Biology
Kristina Tugaeva, Dorothy E. D. P. Hawkins, Jake L. R. Smith, Oliver W. Bayfield, De-Sheng Ker, Andrey A. Sysoev, Oleg Klychnikov, Alfred A. Antson, Nikolai N. Sluchanko
Summary: Phosphorylated SARS-CoV-2 N protein binds to 14-3-3 protein, potentially playing a crucial role in nucleocytoplasmic shuttling and other functions. A critical phosphorylation site located within the SR-rich region of N, which is conserved among related coronaviruses, interacts with all seven human 14-3-3 isoforms.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Plant Sciences
Mahasakthy-Vijeyasri Satyaveanthan, Saidi-Adha Suhaimi, Chyan Leong Ng, Noor-Dina Muhd-Noor, Alias Awang, Kok Wai Lam, Maizom Hassan
Summary: The study presents the purification and characterization of recombinant Theobroma cacao farnesol dehydrogenase enzyme, which catalyzes the oxidation of farnesol to farnesal. The enzyme was extensively characterized in terms of amino acid sequences, phylogeny, substrate specificity, and kinetic parameters. The enzyme showed high specificity for NADP(+) as a coenzyme and trans, trans-farnesol as the preferred substrate, indicating its potential as a NADP(+)-dependent farnesol dehydrogenase.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Microbiology
De-Sheng Ker, Huw T. Jenkins, Sandra J. Greive, Alfred A. Antson
Summary: The study reports the first cryoEM structure of a Henipavirus RNA-bound nucleocapsid assembly, revealing the composition of its helical assembly and the wrapping of RNA. The structure shows similarities and differences with other members of the Paramyxoviridae family and the evolutionarily distant Filoviridae Ebola virus.
Article
Biochemistry & Molecular Biology
Herman K. H. Fung, Shelley Grimes, Alexis Huet, Robert L. Duda, Maria Chechik, Joseph Gault, Carol Robinson, Roger W. Hendrix, Paul J. Jardine, James F. Conway, Christoph G. Baumann, Alfred A. Antson
Summary: Many cellular processes rely on substrate rotation or translocation by a multi-subunit, ring-type NTPase. Researchers have reconstituted a cos packaging system and provided a detailed description of its biochemical and structural properties, revealing similarities and differences in its mechanism and regulation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Kristina Tugaeva, Andrey A. Sysoev, Anna A. Kapitonova, Jake L. R. Smith, Phillip Zhu, Richard B. Cooley, Alfred A. Antson, Nikolai N. Sluchanko
Summary: Phosphorylation of SARS-CoV-2 nucleoprotein recruits human cytosolic 14-3-3 proteins that play a role in virus replication. Using genetic code expansion, it is shown that 14-3-3 binding is triggered by phosphorylation at specific sites on the nucleoprotein. Crystal structures and biochemical data reveal that 14-3-3 binding obstructs a region of the nucleoprotein and inhibits its dephosphorylation. The strength of the 14-3-3/nucleoprotein interaction may be linked to the replicative fitness of the virus.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Mehrnaz Mojtabavi, Sandra J. Greive, Alfred A. Antson, Meni Wanunu
Summary: The application of nanopores as label-free, single-molecule biosensors for structural features in biomolecules has been widely researched. While biological and solid-state nanopores have been extensively used, the study of hybrid nanopores, where an artificial membrane replaces the organic support membrane of proteins, is limited. In this study, a lipid-free hybrid nanopore was developed by connecting a solid-state pore and the G20c portal protein. The chemical functionalization of the synthetic nanopore improved the stability, lifetime, and voltage resilience of the hybrid pore. Additionally, electric-field-driven and motor protein-mediated transport of DNA molecules through the hybrid nanopore was demonstrated. This protein/solid-state device offers potential advantages in sensing and sequencing with higher resolution, signal-to-noise ratio, and throughput compared to conventional membrane-embedded protein platforms.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Oliver W. Bayfield, Andrey N. Shkoporov, Natalya Yutin, Ekaterina V. Khokhlova, Jake L. R. Smith, Dorothy E. D. P. Hawkins, Eugene V. Koonin, Colin Hill, Alfred A. Antson
Summary: CrAssphage and related crassviruses are the most abundant viruses in the human gut, with some individuals having up to 95% of viral sequences from these viruses. By reconstructing Bacteroides intestinalis virus fcrAss001 using cryo-electron microscopy, we gained insights into the structure and function of its proteins. The muzzle protein forms a new fold called the 'crass fold' and acts as a gatekeeper for controlling cargo release. Additionally, the fcrAss001 virus provides ample storage space for cargo proteins in both the capsid and the tail, with a mechanism for protein ejection involving partial unfolding during extrusion through the tail.
Article
Biochemistry & Molecular Biology
Dorothy E. D. P. Hawkins, Oliver W. Bayfield, Herman K. H. Fung, Daniel N. Grba, Alexis Huet, James F. Conway, Alfred A. Antson
Summary: Double-stranded DNA viruses utilize terminase proteins to package viral DNA into the capsid. In this study, the first structural data for a cos virus DNA packaging motor was presented, showing the assembly of terminase proteins, procapsids with the portal protein, and DNA with a cos site. The cryo-EM structure revealed the termination state of packaging and the asymmetry induced by the binding of large terminase/DNA.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Rubashiny Veeramohan, Arief Izzairy Zamani, Kamalrul Azlan Azizan, Hoe-Han Goh, Wan Mohd Aizat, Mohd Fauzi Abd Razak, Nur Sabrina Mohd Yusof, Sharif Mahsufi Mansor, Syarul Nataqain Baharum, Chyan Leong Ng
Summary: This study investigated the secondary metabolite composition of Mitragyna speciosa leaves in different maturity stages using LC-ESI-TOF-MS. The results identified 86 putatively annotated metabolite features, including alkaloids, flavonoids, terpenoids, phenylpropanoids, carboxylic acids, glucosides, phenols, and phenolic aldehydes. The multivariate analysis showed a significant difference in metabolite levels between young and mature leaves. Several new alkaloids were tentatively identified, highlighting the diverse biological activities of M. speciosa. These findings contribute to a better understanding of its pharmaceutical potential.
Meeting Abstract
Biochemistry & Molecular Biology
K. Tugaeva, D. E. D. P. Hawkins, J. L. R. Smith, O. W. Bayfield, D. Ker, A. A. Sysoev, O. I. Klychnikov, R. B. Cooley, A. A. Antson, N. N. Sluchanko