Review
Biochemistry & Molecular Biology
Peipei Yin, Yi Zhang, Lingguang Yang, Yue Feng
Summary: Bacteria and archaea have developed the CRISPR-Cas system as an adaptive defense mechanism against mobile genetic elements, but these elements have also evolved anti-CRISPR proteins to counteract the immune defenses. This review focuses on the non-canonical inhibition strategies adopted by these proteins and provides insights into the ongoing arms race between prokaryotic hosts and their predators.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Microbiology
Chuan Wang, Yuze Yang, Shaoqing Tang, Yuanzi Liu, Yaqin Wei, Xuerui Wan, Yajuan Liu, Zhao Zhang, Yongjie Sunkang
Summary: The study investigates the relationship between the CRISPR-Cas system and the optimum growth temperature in thermophilic bacteria. It reveals that the number of CRISPR loci and the structural features of the repeat sequences are correlated with temperature.
Article
Multidisciplinary Sciences
Akihiro Kawamoto, Tomoko Miyata, Fumiaki Makino, Miki Kinoshita, Tohru Minamino, Katsumi Imada, Takayuki Kato, Keiichi Namba
Summary: The bacterial flagellar MS ring is a core transmembrane complex within the flagellar basal body. CryoEM analysis suggests that the MS ring is formed by 34 full-length FliF subunits, with 23- and 11-fold subsymmetries in the inner and middle M ring, respectively.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Helen B. Belato, George P. Lisi
Summary: The discovery of protein inhibitors of CRISPR-Cas systems, called anti-CRISPRs (Acrs), has revolutionized the field of CRISPR-Cas technology. These inhibitors have diverse structures and functions, and can act as orthosteric or allosteric inhibitors, as well as modify CRISPR-Cas components. Understanding the mechanisms of Acrs is crucial for the development of more precise and controllable CRISPR-Cas tools.
Review
Biotechnology & Applied Microbiology
Jing Wang, Xifang Yang, Xueliang Wang, Wanhe Wang
Summary: CRISPR/Cas-based biosensors have been widely used for nucleic acid detection, but their applications for protein detection have been overlooked. Recent studies show that CRISPR/Cas-based biosensors not only analyze proteins, but also enhance the sensitivity and specificity of protein detection. However, there is a lack of comprehensive reviews and elucidation of the mechanisms of CRISPR/Cas-based biosensors for protein detection, which hinders the development of better protein biosensors.
BIOENGINEERING-BASEL
(2022)
Article
Biochemical Research Methods
Xiaoqiang Huang, Jun Zhou, Dongshan Yang, Jifeng Zhang, Xiaofeng Xia, Yuqing Eugene Chen, Jie Xu
Summary: This study describes a universal computational protein design framework (UniDesign) for designing protein-nucleic acid interactions, and applies it to decode the PAMPIAA interactions in CRISPRCas proteins. The results show that UniDesign can accurately capture the natural preferences of PAMs and PIAAs, making it a useful tool for engineering CRISPRCas and other nucleic acid-interacting proteins.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Claudia Alvarez-Carreno, Petar Penev, Anton S. Petrov, Loren Dean Williams
Summary: The SH3 and OB domains are the simplest, oldest, and most common protein domains in the translation system. These domains share a common core region with significant structure and sequence similarity, suggesting they share a common ancestor. The OB domain likely evolved from duplication and adaptation of the SH3 domain core, or vice versa, in a simple and probable transformation.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Review
Biochemistry & Molecular Biology
Kevin Bloh, Natalia Rivera-Torres
Summary: The mechanism of ssODN-directed gene editing has been a topic of discussion within the field of CRISPR gene editing. The ExACT pathway, based on oligo-driven DNA repair, provides a comprehensive understanding of the different ways DNA repair can occur in the presence of a repair oligonucleotide after CRISPR cleavage, by comparing and challenging other similar DNA repair pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Shanshan Yang, Jian Huang, Bifang He
Summary: CRISPR-Cas systems play a key role in prokaryotic adaptive immune system and have been utilized in eukaryotic gene editing. Cas proteins, as an important component, are essential for distinguishing different types of CRISPR-Cas systems. Accurate prediction and identification of Cas proteins contribute to inferring the type of CRISPR-Cas systems and advancing genome editing.
Article
Biochemistry & Molecular Biology
Pascal Markle, Lisa-Katharina Maier, Sandra Maass, Claudia Hirschfeld, Jurgen Bartel, Dorte Becher, Bjorn Voss, Anita Marchfelder
Summary: This study focused on a small RNA (s479) from the halophilic archaeon Haloferax volcanii and revealed its crucial role in regulating zinc transport. s479 was found to directly interact with the target gene znuC1 mRNA, leading to the upregulation of relevant genes. Interestingly, s479 was also suggested to be linked to the CRISPR-Cas system based on experimental results with Cas protein deletion strains.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Nagaraj Bharathkumar, Abraham Sunil, Prabhakar Meera, Sam Aksah, Muthu Kannan, Konda Mani Saravanan, Thirunavukarasou Anand
Summary: The CRISPR-Cas genome editing system, part of a bacteria-based immune system, has opened up new possibilities in gene editing with the discovery of Cas proteins like Cas9, Cas12a, and Cas13. Ongoing research aims to explore the efficacy and safety of CRISPR for various applications, including therapeutic uses.
MOLECULAR BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Shuo Huang, Rui Dai, Zhiqi Zhang, Han Zhang, Meng Zhang, Zhangjun Li, Kangrui Zhao, Wenjun Xiong, Siyu Cheng, Buhua Wang, Yi Wan
Summary: CRISPR/Cas systems are widely used in gene editing due to their accuracy, programmability, ease of use, and affordability. Additionally, they have been applied in live-cell imaging and bioanalysis, expanding the scope of their use beyond gene editing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Physical
Noshad Peyravian, Maziar Malekzadeh Kebria, Jafar Kiani, Peiman Brouki Milan, Masoud Mozafari
Summary: This review focuses on the recent advancements of microfluidic systems to deliver CRISPR/Cas systems in clinical and therapy investigations, highlighting the limitations of conventional delivery tools and the advantages of microfluidic systems in in vitro delivery.
Article
Biochemistry & Molecular Biology
Sooyeon Song, Ekaterina Semenova, Konstantin Severinov, Laura Fernandez-Garcia, Michael J. Benedik, Toshinari Maeda, Thomas K. Wood
Summary: This study reveals the activity of the CRISPR-Cas system in Escherichia coli and its role in inhibiting cryptic prophages through RNA interference. These findings provide new insights into the function of the CRISPR-Cas system in bacteria.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jiaxue Zhao, Yanyan Xi, Jiangfeng Zhang, Yuefei Jin, Haiyan Yang, Guangcai Duan, Shuaiyin Chen, Jinzhao Long
Summary: This study investigated the prevalence and diversity of CRISPR/Cas systems in 175 Klebsiella oxytoca strains. It was found that 58.86% of the strains possessed at least one confirmed CRISPR locus, with the I-F system being the most prevalent. The IV-A3 system was randomly distributed and could be divided into two subgroups. Space origin analysis revealed significant matches between some spacer sequences and mobile genetic elements. The phage tail tape measure protein and conjunctive transfer system protein were identified as important targets of the I-F and IV-A3 systems, respectively. The predicted PAM sequences for the different systems were also identified.
MOLECULAR GENETICS AND GENOMICS
(2023)
Article
Biochemistry & Molecular Biology
Tautvydas Karvelis, Greta Bigelyte, Joshua K. Young, Zhenglin Hou, Rimante Zedaveinyte, Karolina Budre, Sushmitha Paulraj, Vesna Djukanovic, Stephen Gasior, Arunas Silanskas, Ceslovas Venclovas, Virginijus Siksnys
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Kira S. Makarova, Albertas Timinskas, Yuri Wolf, Ayal B. Gussow, Virginijus Siksnys, Ceslovas Venclovas, Eugene Koonin
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Darius Kazlauskas, Mart Krupovic, Julien Guglielmini, Patrick Forterre, Ceslovas Venclovas
NUCLEIC ACIDS RESEARCH
(2020)
Article
Endocrinology & Metabolism
Maris Laan, Laura Kasak, Kestutis Timinskas, Marina Grigorova, Ceslovas Venclovas, Alexandre Renaux, Tom Lenaerts, Margus Punab
Summary: This study identified the genetic basis of partial gonadal dysgenesis (PGD) in a non-consanguineous family from Estonia, with some patients carrying the NR5A1 c.991-1G > C mutation. Segregation analysis showed incomplete penetrance and phenotypic variability among carriers of this mutation, with possible modulation by rare heterozygous variants inherited from the other parent. The study also identified a likely pathogenic variant SOS1 p.Y136H in another patient, supporting a distinct genetic cause for their condition.
CLINICAL ENDOCRINOLOGY
(2021)
Article
Biochemical Research Methods
Ilia Igashov, Kliment Olechnovic, Maria Kadukova, Ceslovas Venclovas, Sergei Grudinin
Summary: This study introduces VoroCNN, a deep convolutional neural network based on Voronoi tessellation, for predicting local qualities of 3D protein folds. The prediction results of VoroCNN are competitive and superior to previous 3D CNN architectures for the same task. The study also discusses practical applications of VoroCNN, such as in recognizing protein binding interfaces.
Article
Biochemistry & Molecular Biology
Marc F. Lensink, Guillaume Brysbaert, Theo Mauri, Nurul Nadzirin, Sameer Velankar, Raphael A. G. Chaleil, Tereza Clarence, Paul A. Bates, Ren Kong, Bin Liu, Guangbo Yang, Ming Liu, Hang Shi, Xufeng Lu, Shan Chang, Raj S. Roy, Farhan Quadir, Jian Liu, Jianlin Cheng, Anna Antoniak, Cezary Czaplewski, Artur Gieldon, Mateusz Kogut, Agnieszka G. Lipska, Adam Liwo, Emilia A. Lubecka, Martyna Maszota-Zieleniak, Adam K. Sieradzan, Rafal Slusarz, Patryk A. Wesolowski, Karolina Zieba, Carlos A. Del Carpio Munoz, Eiichiro Ichiishi, Ameya Harmalkar, Jeffrey J. Gray, Alexandre M. J. J. Bonvin, Francesco Ambrosetti, Rodrigo Vargas Honorato, Zuzana Jandova, Brian Jimenez-Garcia, Panagiotis I. Koukos, Siri Van Keulen, Charlotte W. Van Noort, Manon Reau, Jorge Roel-Touris, Sergei Kotelnikov, Dzmitry Padhorny, Kathryn A. Porter, Andrey Alekseenko, Mikhail Ignatov, Israel Desta, Ryota Ashizawa, Zhuyezi Sun, Usman Ghani, Nasser Hashemi, Sandor Vajda, Dima Kozakov, Mireia Rosell, Luis A. Rodriguez-Lumbreras, Juan Fernandez-Recio, Agnieszka Karczynska, Sergei Grudinin, Yumeng Yan, Hao Li, Peicong Lin, Sheng-You Huang, Charles Christoffer, Genki Terashi, Jacob Verburgt, Daipayan Sarkar, Tunde Aderinwale, Xiao Wang, Daisuke Kihara, Tsukasa Nakamura, Yuya Hanazono, Ragul Gowthaman, Johnathan D. Guest, Rui Yin, Ghazaleh Taherzadeh, Brian G. Pierce, Didier Barradas-Bautista, Zhen Cao, Luigi Cavallo, Romina Oliva, Yuanfei Sun, Shaowen Zhu, Yang Shen, Taeyong Park, Hyeonuk Woo, Jinsol Yang, Sohee Kwon, Jonghun Won, Chaok Seok, Yasuomi Kiyota, Shinpei Kobayashi, Yoshiki Harada, Mayuko Takeda-Shitaka, Petras J. Kundrotas, Amar Singh, Ilya A. Vakser, Justas Dapkunas, Kliment Olechnovic, Ceslovas Venclovas, Rui Duan, Liming Qiu, Xianjin Xu, Shuang Zhang, Xiaoqin Zou, Shoshana J. Wodak
Summary: The results of the CAPRI Round 50 showed that 25 groups participated in submitting models for 12 targets, with a good level of accuracy overall.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Justas Dapkunas, Kliment Olechnovic, Ceslovas Venclovas
Summary: The goal of CASP experiments is to monitor progress in protein structure prediction by testing capabilities of predicting protein complex structures. Models of protein assemblies were generated through template-based modeling and free docking, emphasizing the importance of interaction interfaces in modeling and scoring.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Andriy Kryshtafovych, John Moult, Wendy M. Billings, Dennis Della Corte, Krzysztof Fidelis, Sohee Kwon, Kliment Olechnoyic, Chaok Seok, Ceslovas Venclovas, Jonghun Won
Summary: CASP aims to advance protein structure prediction technology and successfully conducted a project to compute the structures of proteins in the SARS-CoV-2 genome. Models from the AlphaFold2 group showed good agreement with experimental structures.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
Tautvydas Karvelis, Gytis Druteika, Greta Bigelyte, Karolina Budre, Rimante Zedaveinyte, Arunas Silanskas, Darius Kazlauskas, Ceslovas Venclovas, Virginijus Siksnys
Summary: This study reveals that TnpB of Deinococcus radiodurans ISDra2 is an RNA-directed nuclease guided by an RNA from the right-end element of a transposon to cleave DNA next to the 5'-TTGAT transposon-associated motif. The research also demonstrates that TnpB can be reprogrammed to cleave DNA target sites in human cells. These findings highlight the role of TnpB in transposition, confirm that TnpB is a functional precursor of CRISPR-Cas nucleases, and establish TnpB as a prototype for a new genome editing system.
Article
Microbiology
Mindaugas Zaremba, Donata Dakineviciene, Edvardas Golovinas, Evelina Zagorskaite, Edvinas Stankunas, Anna Lopatina, Rotem Sorek, Elena Manakova, Audrone Ruksenaite, Arunas Silanskas, Simonas Asmontas, Algirdas Grybauskas, Ugne Tylenyte, Edvinas Jurgelaitis, Rokas Grigaitis, Kestutis Timinskas, Ceslovas Venclovas, Virginijus Siksnys
Summary: This study shows that the short pAgo of Geobacter sulfurreducens forms a stable heterodimeric complex with the NAD(+)-bound Sir2 protein. The complex is believed to recognize invading plasmid or phage DNA, activate the Sir2 subunit, trigger NAD(+) depletion, and prevent DNA propagation. In vitro experiments demonstrate that the activated complex functions as a NADase that hydrolyses NAD(+) to ADPR.
NATURE MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Giedrius Sasnauskas, Giedre Tamulaitiene, Gytis Druteika, Arturo Carabias, Arunas Silanskas, Darius Kazlauskas, Ceslovas Venclovas, Guillermo Montoya, Tautvydas Karvelis, Virginijus Siksnys
Summary: The TnpB proteins of the IS200/IS605 transposon family have been discovered as the smallest RNA-guided nucleases capable of targeted genome editing in eukaryotic cells. They are likely predecessors of Cas12 nucleases, which are widely used for targeted genome manipulation. This study presents the cryogenic-electron microscopy structures of the Deinococcus radiodurans TnpB-reRNA complex, revealing the basic architecture and molecular mechanism of TnpB nuclease for DNA target recognition and cleavage.
Article
Biochemistry & Molecular Biology
Kliment Olechnovic, Ceslovas Venclovas
Summary: VoroIF-GNN is a novel method that assesses inter-subunit interfaces in a protein-protein complex structural model solely based on the input structure. It derives interface contacts from the Voronoi tessellation of atomic balls, constructs a contact graph, and predicts the accuracy of each contact using an attention-based GNN. The method performs well in selecting the best multimeric model out of many in blind tests during CASP15.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemical Research Methods
Hugo Schweke, Qifang Xu, Gerardo Tauriello, Lorenzo Pantolini, Torsten Schwede, Frederic Cazals, Alix Lheritier, Juan Fernandez-Recio, Luis Angel Rodriguez-Lumbreras, Ora Schueler-Furman, Julia. K. K. Varga, Brian Jimenez-Garcia, Manon F. Reau, Alexandre M. J. J. Bonvin, Castrense Savojardo, Pier-Luigi Martelli, Rita Casadio, Jerome Tubiana, Haim. J. J. Wolfson, Romina Oliva, Didier Barradas-Bautista, Tiziana Ricciardelli, Luigi Cavallo, Ceslovas Venclovas, Kliment Olechnovic, Raphael Guerois, Jessica Andreani, Juliette Martin, Xiao Wang, Genki Terashi, Daipayan Sarkar, Charles Christoffer, Tunde Aderinwale, Jacob Verburgt, Daisuke Kihara, Anthony Marchand, Bruno E. Correia, Rui Duan, Liming Qiu, Xianjin Xu, Shuang Zhang, Xiaoqin Zou, Sucharita Dey, Roland L. Dunbrack, Emmanuel D. Levy, Shoshana J. Wodak
Summary: A benchmark dataset comprising 1677 homodimer protein crystal structures was created and evaluated using 252 scoring functions. A consensus score and a cross-validated Random Forest classifier generated excellent performance, surpassing individual scores developed by different groups. The accuracy of AlphaFold2 engines also supported the reliability of the benchmark dataset annotations. Optimizing the combined power of interface scoring functions and evaluating them on challenging benchmark datasets appears to be a promising strategy.
Article
Biology
Sophia Gessner, Zela Alexandria-Mae Martin, Michael A. Reiche, Joana A. Santos, Ryan Dinkele, Atondaho Ramudzuli, Neeraj Dhar, Timothy J. de Wet, Saber Anoosheh, Dirk M. Lang, Jesse Aaron, Teng-Leong Chew, Jennifer Herrmann, Rolf Mueller, John D. McKinney, Roger Woodgate, Valerie Mizrahi, Ceslovas Venclovas, Meindert H. Lamers, Digby F. Warner
Summary: A study found that a DNA damage-inducible mutagenic gene cassette is involved in the emergence of drug resistance in Mycobacterium tuberculosis. The study also revealed the molecular composition and operation of the encoded 'mycobacterial mutasome'. These findings provide a new target for the development of adjunctive therapeutics to protect anti-TB drugs against emerging resistance.
Meeting Abstract
Biochemistry & Molecular Biology
Justas Dapkunas, Albertas Timinskas, Kliment Olechnovic, Migle Tomkuviene, Ceslovas Venclovas
