Article
Chemistry, Multidisciplinary
Ashraya Ravikumar, Mrugsen Nagsen Gopnarayan, Sriram Subramaniam, Narayanaswamy Srinivasan
Summary: This study evaluates systematic differences in local structure and conformation within protein tertiary structures determined by crystallography and cryo-EM. The results show that cryo-EM structures have more dispersed side chains compared to X-ray crystallography structures of similar resolution. This trend is observed in both subunit interface packing and within the core of tertiary structures. The reduced dispersion of side chains in protein crystals could be attributed to dehydration in 3D crystals prepared for X-ray crystallography, while the higher freezing rate in cryo-EM samples may preserve a more native conformation.
Article
Multidisciplinary Sciences
Oliver F. Harder, Sarah V. Barrass, Marcel Drabbels, Ulrich J. Lorenz
Summary: Microsecond time-resolved cryo-EM allows for observation of fast protein dynamics, as demonstrated by the contraction of the CCMV capsid induced by a pH jump.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Blake T. Riley, Stephanie A. Wankowicz, Saulo H. P. de Oliveira, Gydo C. P. van Zundert, Daniel W. Hogan, James S. Fraser, Daniel A. Keedy, Henry van den Bedem
Summary: The new qFit 3 software automates the analysis of dynamic protein structure data by generating a multi-conformer model, providing important insights for biological research. The software has been improved to run efficiently on small servers, desktops, or laptops. qFit 3 is open-source and available at the specified URL.
Article
Biochemistry & Molecular Biology
Klaudia Chmelova, Tadeja Gao, Martin Polak, Andrea Schenkmayerova, Tristan I. Croll, Tanvir R. Shaikh, Jana Skarupova, Radka Chaloupkova, Kay Diederichs, Randy J. Read, Jiri Damborsky, Jiri Novacek, Martin Marek
Summary: Haloalkane dehalogenase (HLD) enzymes have been extensively studied for their ability to remove halogen substituents in organic compounds. In this study, the structural organization of a subfamily III HLD-like enzyme called DhmeA was investigated using cryo-electron microscopy and x-ray crystallography. It was found that DhmeA forms diverse quaternary structures, ranging from small oligomers to large supramolecular ring-like assemblies. The crystal structure revealed a 20-mer ring-like structure with specific symmetries, showing a negatively charged exterior and a positively charged interior. These findings suggest that DhmeA may play a role in processing large negatively charged macromolecular substrates.
Article
Virology
Mallika Sastry, Anita Changela, Jason Gorman, Kai Xu, Gwo-Yu Chuang, Chen-Hsiang Shen, Cheng Cheng, Hui Geng, Sijy O'Dell, Li Ou, Reda Rawi, Mateo Reveiz, Guillaume B. E. Stewart-Jones, Shuishu Wang, Baoshan Zhang, Tongqing Zhou, Andrea Biju, Michael Chambers, Xuejun Chen, Angela R. Corrigan, Bob C. Lin, Mark K. Louder, Krisha McKee, Alexandra F. Nazzari, Adam S. Olia, Danealle K. Parchment, Edward K. Sarfo, Tyler Stephens, Jonathan Stuckey, Yaroslav Tsybovsky, Raffaello Verardi, Yiran Wang, Cheng-Yan Zheng, Yuling Chen, Nicole A. Doria-Rose, Adrian B. McDermott, John R. Mascola, Peter D. Kwong
Summary: Vaccine regimens incorporating diverse fusion peptide-conjugates and Env trimers with variation in fusion peptide length and sequence can enhance neutralizing responses and generate diverse neutralizing antibodies in mice and guinea pigs. These findings provide insight for HIV-1 vaccine development.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Stavros Azinas, Marta Carroni
Summary: Cryo-EM is a major tool for determining protein structures, while AlphaFold2 enables high-confidence atomic models for polypeptide chains. Cryo-EM retains unique characteristics for determining structures of macromolecular complexes, allowing for near-atomic structures and exploring conformational panoramas. It also has the potential to develop a structural proteomic approach using ex vivo specimens.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Hadiatullah Hadiatullah, Zhao He, Zhiguang Yuchi
Summary: This review summarizes recent advances in the study of high-resolution structures of ryanodine receptors (RyRs) and discusses the gating mechanisms, regulatory mechanisms, and the impact of disease-causing mutations on the structure and function of RyRs. The structural information obtained could contribute to the diagnosis and development of pharmacological therapies for related diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yukie Kamitsukasa, Kenji Nakano, Karin Murakami, Kunio Hirata, Masaki Yamamoto, Toshiyuki Shimizu, Umeharu Ohto
Summary: Nucleotide-binding and oligomerization domain-like receptors NLRP9 can form inflammasomes and activate immune responses during viral infection, but little is known about its mechanism. This study provides structural insights into NLRP9's inactive and closed conformations, as well as its unique C-terminal region that may play a role in its specific function.
Article
Multidisciplinary Sciences
Tsehai A. J. Grell, Mark Mason, Aaron A. Thompson, Jose Carlos Gomez-Tamayo, Daniel Riley, Michelle V. Wagner, Ruth Steele, Rodrigo F. Ortiz-Meoz, Jay Wadia, Paul L. Shaffer, Gary Tresadern, Sujata Sharma, Xiaodi Yu
Summary: Malic enzymes play crucial roles in cellular energy regulation, redox homeostasis, and biosynthetic processes. Among the three isoforms, ME3 is identified as a therapeutic target for pancreatic cancers. Structural analysis reveals ME3 exists in a stable tetramer in an open form, with its dynamic Domain C being critical for activity, and it does not require modulators for activity.
Article
Biochemistry & Molecular Biology
Juan C. Canul-Tec, Anand Kumar, Jonathan Dhenin, Reda Assal, Pierre Legrand, Martial Rey, Julia Chamot-Rooke, Nicolas Reyes
Summary: Excitatory amino acid transporters (EAATs) play a crucial role in maintaining glutamate gradients in the brain for neurotransmission and preventing neuronal death. The study reveals that Ca2+ competes for a conserved Na+ site at the synapse, while H+ stabilizes substrate occlusion. The mechanism involving K+ excludes the transmitter during the transport cycle to prevent its neurotoxic release.
Review
Pharmacology & Pharmacy
Maria V. Yelshanskaya, Alexander I. Sobolevsky
Summary: This article summarizes the breakthroughs in molecular characterization of TRPV channels achieved by structural biology techniques, and provides a classification of the identified binding sites in TRPV channels. The combination of mutagenesis, functional recordings, and molecular dynamics simulations further enhances our understanding of the molecular mechanisms of ligand action.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Virology
Morgan E. Abernathy, Kim-Marie A. Dam, Shannon R. Esswein, Claudia A. Jette, Pamela J. Bjorkman
Summary: Global viral infections like H1N1, MERS, Ebola, Zika, and COVID-19 have highlighted the importance of rapidly developing safe and effective vaccines and therapies. Structural biology methods play a crucial role in understanding how antibodies target viral proteins, guiding the design of vaccines and monoclonal antibodies.
Article
Cell Biology
Manickam Gurusaran, Jelle J. Biemans, Christopher W. Wood, Owen R. Davies
Summary: The LINC complex is crucial for maintaining nuclear morphology and transmitting forces in meiosis and somatic cells. The crystal structure of SUN1's luminal region provides insight into its composition and suggests the presence of flexible domains and potential domain-swap interactions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Engineering, Electrical & Electronic
Harshit Gupta, Michael T. McCann, Laurene Donati, Michael Unser
Summary: CryoGAN is a new paradigm for single-particle cryo-electron microscopy reconstruction based on unsupervised deep adversarial learning, achieving 3D structure reconstruction via distribution matching and skipping pose estimation or marginalization. It has shown success in recovering correct structures in an idealized mathematical model and achieving 10.8 angstrom resolution on a realistic synthetic dataset.
IEEE TRANSACTIONS ON COMPUTATIONAL IMAGING
(2021)
Review
Biochemistry & Molecular Biology
Solomon Tsegaye, Gobena Dedefo, Mohammed Mehdi
Summary: The main goal of structural biology is to model proteins and other biological macromolecules, linking structural information to function and dynamics. Understanding the conformational dynamics of protein molecules and nucleic acids is crucial for their biological functions. Various biophysical techniques such as X-ray crystallography, NMR, and cryo-EM are used to solve atomic-resolution structural information, providing insights into the mechanisms of action of biological macromolecules.
BIOLOGICAL CHEMISTRY
(2021)