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
Virology
Mario Mietzsch, Joshua A. Hull, Victoria E. Makal, Alberto Jimenez Ybargollin, Jennifer C. Yu, Kedrick McKissock, Antonette Bennett, Judit Penzes, Bridget Lins-Austin, Qian Yu, Paul Chipman, Nilakshee Bhattacharya, Duncan Sousa, David Strugatsky, Peter Tijssen, Robert McKenna, Mavis Agbandje-McKenna
Summary: AAVs are commonly used in gene therapy, but the presence of preexisting antibodies in the general population poses a challenge. This study investigated a potential alternative, serpentine AAV (SAAV), and found that it shares common features with other AAVs while also being recognized by some human antibodies despite its reptilian origin. This information is valuable for future gene delivery applications and expanding the understanding of AAV capsid structures.
JOURNAL OF VIROLOGY
(2022)
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
Nanoscience & Nanotechnology
Arjun Rana, Chen-Ting Liao, Ezio Iacocca, Ji Zou, Minh Pham, Xingyuan Lu, Emma-Elizabeth Cating Subramanian, Yuan Hung Lo, Sinead A. Ryan, Charles S. Bevis, Robert M. M. Karl Jr, Andrew J. Glaid, Jeffrey Rable, Pratibha Mahale, Joel Hirst, Thomas Ostler, William Liu, Colum M. O'Leary, Young-Sang Yu, Karen Bustillo, Hendrik Ohldag, David A. Shapiro, Sadegh Yazdi, Thomas E. Mallouk, Stanley J. Osher, Henry C. Kapteyn, Vincent H. Crespi, John V. Badding, Yaroslav Tserkovnyak, Margaret M. Murnane, Jianwei Miao
Summary: The researchers successfully created 138 stable magnetic monopoles on a ferromagnetic meta-lattice and used soft X-ray vector ptycho-tomography to determine their magnetization vector and emergent magnetic field. The study found that the distances between monopole-anti-monopole pairs, monopole-monopole pairs, and anti-monopole-anti-monopole pairs were 18.3 +/- 1.6 nm, 36.1 +/- 2.4 nm, and 43.1 +/- 2.0 nm, respectively. This work demonstrates the potential of ferromagnetic meta-lattices as a platform for studying the interactions and dynamics of magnetic monopoles, and the broad application of soft X-ray vector ptycho-tomography for quantitatively imaging 3D vector fields in magnetic and anisotropic materials at the nanoscale.
NATURE NANOTECHNOLOGY
(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)
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
Biology
Krishan K. Pandey, Sibes Bera, Ke Shi, Michael J. Rau, Amarachi V. Oleru, James A. J. Fitzpatrick, Alan N. Engelman, Hideki Aihara, Duane P. Grandgenett
Summary: Pandey, Bera, Shi et al. reported the cryo-electron microscopy structure of the Rous sarcoma virus octameric intasome complex stabilized by a HIV-1 integrase strand transfer inhibitor. This new structure highlighted the intrinsic flexibility of the distal integrase subunits and proposed ordered conformational transitions within the conserved intasome core during the assembly process.
COMMUNICATIONS BIOLOGY
(2021)
Review
Microbiology
Xiaoying Yu, Erica Ollmann Saphire
Summary: This article reviews the recent developments in the research of filoviruses, particularly ebolaviruses and marburgviruses. It focuses on the discovery and functional characterization of therapeutic monoclonal antibodies targeting the glycoprotein GP of these viruses, as well as the structural insights guiding vaccine development.
Article
Biochemistry & Molecular Biology
Cong Xu, Wenyu Han, Yao Cong
Summary: Since the COVID-19 pandemic began, cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) have been shown to be powerful tools in studying the structure of SARS-CoV-2 spike protein and the intact virion, as well as understanding receptor binding and antibody neutralization. They have also provided insights into the enhanced transformation and immune evasion of variants, aiding in the discovery of antibodies and drugs. This review summarizes the contributions of cryo-EM and cryo-ET in revealing the structures and mechanisms of SARS-CoV-2, as well as their potential in developing vaccines and therapeutics against emerging variants.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Review
Oncology
Puja Bhattacharyya, Richard I. Christopherson, Kristen K. Skarratt, Jake Z. Chen, Thomas Balle, Stephen J. Fuller
Summary: B cells are key players in adaptive immunity, providing long-lasting immune protection after infection. The activation of B cells is mediated by a cell surface receptor called B cell receptor (BCR) upon recognition of an antigen. Abnormal signaling of the BCR and its co-receptors, such as CD22, CD19, and CD81, contributes to the development of B cell malignancies and autoimmune diseases. Recent advancements in cryo-electron microscopy (cryo-EM) and crystallography have provided high-resolution structures of the BCR and its co-receptors, which enhance our understanding of current antibody therapies and facilitate the development of engineered antibodies for the treatment of B cell malignancies and autoimmune diseases.
Article
Virology
Mila M. Leuthold, Turgay Kilic, Jessica M. Devant, Oscar Landeta, Francisco Parra, Kevin P. Dalton, Grant S. Hansman
Summary: This study provides the structural basis for the specificity of an RHDV GI.2 diagnostic antibody (2D9) and explains how amino acid variation at the binding site restricts cross-reactivity. The findings have implications for characterizing antigenic variants and developing new monoclonal antibodies for diagnostics and therapeutics.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hyeongseop Jeong, Youngmin Park, Sooji Song, Kyungmin Min, Jae-Sung Woo, Young-Ho Lee, Eun-Ju Sohn, Sangmin Lee
Summary: Research indicates that VLPs, as a safe drug/vehicle candidate, have great potential in the fields of preventive medicine and therapeutics. Scientists propose that rAMV-CP VLP, based on efficient VLP production process and high-resolution structure analysis, can serve as a useful platform for the development of various new drugs.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biology
Samantha R. Hartmann, Andrew J. Charnesky, Simon P. Fruh, Robert A. Lopez-Astacio, Wendy S. Weichert, Nadia DiNunno, Sung Hung Cho, Carol M. Bator, Colin R. Parrish, Susan L. Hafenstein
Summary: This study investigates the immune response of dogs to vaccination using cryo-electron microscopy and computational methods. The results reveal a specific polyclonal immune response in the serum of dogs infected with canine parvovirus and provide insights into the binding of multiple antibodies or ligands to the virus.
COMMUNICATIONS BIOLOGY
(2023)
Article
Virology
Julia Fakhiri, Kai-Philipp Linse, Mario Mietzsch, Man Xu, Marc A. Schneider, Michael Meister, Oliver Schildgen, Paul Schnitzler, Maria Soderlund-Venermo, Mavis Agbandje-McKenna, Dirk Grimma
JOURNAL OF VIROLOGY
(2020)
Article
Immunology
Shanan N. Emmanuel, Mario Mietzsch, Yu Shan Tseng, James Kennon Smith, Mavis Agbandje-McKenna
Summary: Parvoviruses are small DNA viruses that can range from nonpathogenic to pathogenic in humans and animals. Infection with parvovirus triggers the host immune system to produce antibodies to eliminate the virus and prevent reinfection. Efforts are being made to combat the effects of pre-existing or post-treatment antibodies that can hinder therapeutic benefits, and understanding antigenic epitopes can aid in vaccine development and engineering novel capsids.
Article
Biochemistry & Molecular Biology
Mario Mietzsch, Ya Li, Justin Kurian, James Kennon Smith, Paul Chipman, Robert McKenna, Lin Yang, Mavis Agbandje-McKenna
JOURNAL OF STRUCTURAL BIOLOGY
(2020)
Article
Virology
L. Patrick Havlik, Katherine E. Simon, J. Kennon Smith, Kelli A. Klinc, Longping Tse, Daniel K. Oh, Marco M. Fanous, Rita M. Meganck, Mario Mietzsch, Jurgen Kleinschmidt, Mavis Agbandje-McKenna, Aravind Asokan
JOURNAL OF VIROLOGY
(2020)
Article
Virology
Mengxiao Luo, Mario Mietzsch, Paul Chipman, Kangkang Song, Chen Xu, John Spear, Duncan Sousa, Robert McKenna, Maria Soderlund-Venermo, Mavis Agbandje-McKenna
Summary: Human bocaviruses (HBoVs) infect children and immunocompromised individuals, resulting in respiratory and gastrointestinal infections. This study compared the capsid structures of HBoV2 with previously determined HBoV1, HBoV3, and HBoV4, revealing strain and genus-specific features contributing to tissue tropism and antigenicity. Additionally, analyzing HBoV1 and HBoV2 structures under acidic conditions provided insights into capsid changes associated with endosomal and gastrointestinal acidification, unraveling the molecular mechanism of HBoV infection.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Lydia Viney, Tilmann Burckstummer, Courtnee Eddington, Mario Mietzsch, Modassir Choudhry, Tom Henley, Mavis Agbandje-McKenna
Summary: Novel AAV-XV variants have been developed for enhanced cell transduction at low doses, indicating the importance of the AAP coding region in both viral particle assembly and cell infection.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Mario Mietzsch, Ariana Jose, Paul Chipman, Nilakshee Bhattacharya, Nadia Daneshparvar, Robert McKenna, Mavis Agbandje-McKenna
Summary: This study reports the capsid structures of four additional AAV serotypes, completing the structural atlas of AAV capsids. These structures exhibit AAV capsid features and show classification-specific protein loop conformations. The comprehensive characterization of these structures provides valuable insights for future vector engineering efforts to improve gene delivery success.
Article
Virology
Jennifer Chun Yu, Mario Mietzsch, Amriti Singh, Alberto Jimenez Ybargollin, Shweta Kailasan, Paul Chipman, Nilakshee Bhattacharya, Julia Fakhiri, Dirk Grimm, Amit Kapoor, Indre Kucinskaite-Kodze, Aurelija Zvirbliene, Maria Soderlund-Venermo, Robert McKenna, Mavis Agbandje-McKenna
Summary: The study reports the capsid structure of Gorilla bocavirus 1 (GBoV1) and its interactions with human sera and monoclonal antibodies. GBoV1 shares similarities with Human bocavirus 1 (HBoV1) but shows differences in specific structural regions. Furthermore, GBoV1 demonstrates comparable seropositivity rates to HBoV1 when tested against human sera.
Article
Biochemistry & Molecular Biology
Antonette Bennett, Joshua Hull, Nelly Jolinon, Julie Tordo, Katie Moss, Enswert Binns, Mario Mietzsch, Cathleen Hagemann, R. Michael Linden, Andrea Serio, Paul Chipman, Duncan Sousa, Felix Broecker, Peter Seeberger, Els Henckaerts, Robert McKenna, Mavis Agbandje-McKenna
Summary: AAV-TT, a variant of AAV2, shows higher neurotropism compared to wild type AAV2 and is currently being evaluated for central nervous system applications. It differs from AAV2 by 14 amino acids, including R585S and R588T, which have been shown to be essential for heparan sulfate binding of AAV2.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Article
Virology
Mario Mietzsch, Jennifer C. Yu, Jane Hsi, Paul Chipman, Felix Broecker, Zhang Fuming, Robert J. Linhardt, Peter H. Seeberger, Regine Heilbronn, Robert McKenna, Mavis Agbandje-McKenna
Summary: This study utilized cryo-electron microscopy and three-dimensional image reconstruction to map the binding site of LacNAc and monoclonal antibodies on the AAVrh.10 capsid. It was found that LacNAc binds to a pocket on the capsid protrusion, and some anti-AAV8 MAbs cross-react with AAVrh.10, binding to the 3-fold capsid protrusions. The insights gained from this study were used to engineer AAVrh.10 variants capable of evading known neutralizing antibodies, potentially aiding in clinical trials and biologics approval.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Mario Mietzsch, Courtnee Eddington, Ariana Jose, Jane Hsi, Paul Chipman, Tom Henley, Modassir Choudhry, Robert McKenna, Mavis Agbandje-McKenna
Summary: Novel Rep hybrids from different AAV serotypes can significantly reduce the percentage of empty capsids in various AAV serotypes, while improving the yields of genome-containing AAV capsids. These Rep chimeras have the potential to revolutionize rAAV production and enhance the therapeutic efficacy of AAV-based gene therapies.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
L. Patrick Havlik, Anshuman Das, Mario Mietzsch, Daniel K. Oh, Jonathan Ark, Robert McKenna, Mavis Agbandje-McKenna, Aravind Asokan
Summary: New AAV variants with enhanced cellular binding, uptake, and transduction have been evolved through infectious cycling, with one able to recognize sulfated glycosaminoglycans and another switching receptors from AAVR to integrin beta 1. The visualization of the AAVhum.8 capsid revealed a newly acquired integrin recognition motif, providing insights into designing viruses with improved attributes for gene therapy applications.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Joshua A. Hull, Mario Mietzsch, Paul Chipman, David Strugatsky, Robert McKenna
Summary: The study observed the structure of envelope-associated adeno-associated virus (EA-AAV) capsids and found that they showed no significant structural variation compared to non-envelope capsids. The results suggest that MAAP may enhance AAV encapsulation within exosomes.
Article
Virology
Michael Velez, Mario Mietzsch, Jane Hsi, Logan Bell, Paul Chipman, Xiaofeng Fu, Robert Mckenna
Summary: This study investigated the capsid structures of Canine minute virus, Rat bocavirus, and Porcine bocavirus 1 and found conserved features but differences at two- and threefold axes. These results will contribute to future characterization of these viruses.
Article
Virology
Shanan N. Emmanuel, J. Kennon Smith, Jane Hsi, Yu-Shan Tseng, Matias Kaplan, Mario Mietzsch, Paul Chipman, Aravind Asokan, Robert McKenna, Mavis Agbandje-McKenna
Summary: This study mapped the antigenic epitopes of five monoclonal antibodies (MAbs) on AAV9, providing a foundation for the engineering of AAV variant vectors that can bypass preexisting neutralizing antibodies. These engineered AAV9 variants can expand the patient cohort eligible for gene delivery.
JOURNAL OF VIROLOGY
(2022)