Article
Cell Biology
Tian Tian, Lili Chen, Zhen Dou, Zhisen Yang, Xinjiao Gao, Xiao Yuan, Chengliang Wang, Ran Liu, Zuojun Shen, Ping Gui, Maikun Teng, Xianlei Meng, Donald L. Hill, Lin Li, Xuan Zhang, Xing Liu, Linfeng Sun, Jianye Zang, Xuebiao Yao
Summary: This study reveals the molecular basis of how human CCAN interacts with duplex DNA and its importance in accurate chromosome segregation through cryo-electron microscopy and functional analyses.
Article
Biochemistry & Molecular Biology
Xizi Chen, Yanhui Xu
Summary: Researchers have made a breakthrough in determining the structure of TFIID-based PIC complexes, revealing the assembly mechanisms on TATA box and TATA-less promoters and providing a framework for further investigation of transcription initiation.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Xizi Chen, Yilun Qi, Zihan Wu, Xinxin Wang, Jiabei Li, Dan Zhao, Haifeng Hou, Yan Li, Zishuo Yu, Weida Liu, Mo Wang, Yulei Ren, Ze Li, Huirong Yang, Yanhui Xu
Summary: This study elucidates the assembly mechanism of human TFIID-based PIC, showing two tracks for modular reorganization and direct promoter deposition, converging at a holo PIC with around 50 subunits. TFIID stabilizes PIC organization and supports CAK-mediated phosphorylation of Pol II.
Article
Biochemistry & Molecular Biology
Xuehui Li, Huiyan Li, Qian Jing, Mengxue Wang, Tingting Hu, Li Li, Qiuping Zhang, Mengxin Liu, Yu Vincent Fu, Junhong Han, Dan Su
Summary: hSSRP1 is an essential component of the facilitates chromatin transcription complex, with multiple functions such as nuclear localization, histone chaperone activity, DNA binding, and interaction with cellular proteins. The study provides insights into the structural basis for hSSRP1 functionality.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Huirong Yang, Zishuo Yu, Xizi Chen, Jiabei Li, Ningning Li, Jiaxuan Cheng, Ning Gao, Hai-Xin Yuan, Dan Ye, Kun-Liang Guan, Yanhui Xu
Summary: The Tuberous sclerosis complex (TSC) consists of TSC1, TSC2, and TBC1D7 in a 2:2:1 stoichiometry, forming an arch-shaped structure. The complex includes two TSC1 coiled-coils and one TBC1D7 bridging over the TSC2 dimer, showing asymmetry. The TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1, revealing mechanisms of TSC complex assembly and GAP activity.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Yashpal Rawal, Lijia Jia, Aviv Meir, Shuo Zhou, Hardeep Kaur, Eliza A. Ruben, Youngho Kwon, Kara A. Bernstein, Maria Jasin, Alexander B. Taylor, Sandeep Burma, Robert Hromas, Alexander V. Mazin, Weixing Zhao, Daohong Zhou, Elizabeth V. Wasmuth, Eric C. Greene, Patrick Sung, Shaun K. Olsen
Summary: This study reports cryogenic electron microscopy reconstructions of human BCDX2 in apo and ssDNA-bound states. The structures reveal the participation of the amino-terminal domains of RAD51B, RAD51C and RAD51D in inter-subunit interactions for complex formation and ssDNA-binding specificity. Single-molecule DNA curtain analysis provides insights into how BCDX2 enhances RAD51-ssDNA nucleoprotein filament assembly. Additionally, the cryogenic electron microscopy and functional analyses explain how RAD51C alterations found in patients with cancer inactivate DNA binding and the HR mediator activity of BCDX2.
Article
Biochemistry & Molecular Biology
Richard W. Baker, Janice M. Reimer, Peter J. Carman, Bengi Turegun, Tsutomu Arakawa, Roberto Dominguez, Andres E. Leschziner
Summary: The study reveals that the interaction between Sth1 and the nucleosome acidic patch enhances chromatin remodeling function, and large conformational changes are part of Sth1 regulation and RSC assembly.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Tian Xie, Guangjun Xu, Yun Liu, Bradley Quade, Weichun Lin, Xiao-chen Bai
Summary: MuSK is a receptor tyrosine kinase that is essential for the neuromuscular junction. Its activation requires both agrin and LRP4 coreceptors. This study presents the cryo-EM structure of the extracellular ternary complex of agrin/LRP4/MuSK, revealing how LRP4 recruits agrin and MuSK to activate MuSK receptor.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Tian Xie, Guangjun Xu, Yun Liu, Bradley Quade, Weichun Lin, Xiao-chen Bai
Summary: MuSK is a receptor tyrosine kinase that plays a crucial role in the formation and maintenance of the neuromuscular junction. This study reveals the structure of the agrin/LRP4/MuSK ternary complex and uncovers the mechanism of how agrin and LRP4 coactivate the MuSK receptor.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Sisi Li, Tian Xie, Peng Liu, Lei Wang, Xin Gong
Summary: The study presents high-resolution cryo-EM structures of human SPT complex and SPT-ORMDL3 complex, revealing the basis for their assembly and substrate selectivity. These structures provide important insights for understanding sphingolipid homeostasis and development of related therapeutic drugs.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biology
Khushboo Kumari, Siddhartha P. Sarma
Summary: Among the 10 paralogs of the MazEF Toxin-Antitoxin system in Mycobacterium tuberculosis, MazEF6 plays a crucial role in multidrug tolerance, virulence, stress adaptation, and establishment of the Non Replicative Persistant (NRP) state. The study on the solution structures and dynamics of MazE6 and its complex with the cognate operator DNA sheds light on the transcriptional regulation and provides insights for the development of chemotherapeutic agents targeting the MazEF system.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Gaurika Garg, Christian Dienemann, Lucas Farnung, Juliane Schwarz, Andreas Linden, Henning Urlaub, Patrick Cramer
Summary: We provide mechanistic insights into the three major steps of human co-transcriptional pre-mRNA capping based on six different cryo-EM structures. The human mRNA capping enzyme, RNGTT, first docks to the Pol II stalk to position its triphosphatase domain near the RNA exit site. The capping enzyme then moves onto the Pol II surface, and its guanylyltransferase receives the pre-mRNA 5'-diphosphate end.
Article
Biochemistry & Molecular Biology
Yibo Jin, Paul K. Fyfe, Scott Gardner, Stephan Wilmes, Doryen Bubeck, Ignacio Moraga
Summary: IL-27 is an important cytokine that induces immunosuppressive responses. The study reveals the structure of the IL-27 receptor recognition complex and provides insights into the mechanism of IL-27 signaling. These findings contribute to a better understanding of IL-27's function and regulation.
Article
Multidisciplinary Sciences
Man Pan, Qingyun Zheng, Tian Wang, Lujun Liang, Junxiong Mao, Chong Zuo, Ruichao Ding, Huasong Ai, Yuan Xie, Dong Si, Yuanyuan Yu, Lei Liu, Minglei Zhao
Summary: This study reveals the mechanism of the N-degron pathway mediated by Ubr1, including key structural elements involved in the initiation and elongation steps of ubiquitination.
Article
Biology
Sung-Eun Nam, Yiu Wing Sunny Cheung, Thanh Ngoc Nguyen, Michael Gong, Samuel Chan, Michael Lazarou, Calvin K. Yip
Summary: Nam and Cheung et al. describe the structural and biochemical characterization of human autophagy factor EPG5 that functions in autophagosome-lysosome tethering. They show that hEPG5 adopts an extended shepherd's staff architecture, binds preferentially to GABARAP proteins, and is recruited to mitochondria during mitophagy.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Vignesh Kasinath, Curtis Beck, Paul Sauer, Simon Poepsel, Jennifer Kosmatka, Marco Faini, Daniel Toso, Ruedi Aebersold, Eva Nogales
Summary: Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) work together to regulate gene expression and determine cell identity through epigenetic mechanisms. The recruitment of PRC2 by recognition of PRC1-mediated H2AK119ub1 involves cofactors JARID2 and AEBP2, which play important roles in overcoming inhibitory effects on PRC2 activity. The interactions between these cofactors and histone modifications suggest a key role in regulating PRC2 activity.
Article
Biochemistry & Molecular Biology
Igor Asanovi, Emilia Strandback, Alena Kroupova, Djurdja Pasajlic, Anton Meinhart, Pai Tsung-Pin, Nemanja Djokovic, Dorothea Anrather, Thomas Schuetz, Marcin Jozef Suskiewicz, Sirelin Sillamaa, Thomas Kocher, Rebecca Beveridge, Katarina Nikolic, Alexander Schleiffer, Martin Jinek, Markus Hartl, Tim Clausen, Josef Penninger, Peter Macheroux, Stefan Weitzer, Javier Martinez
Summary: The tRNA ligase complex (tRNA-LC) plays a crucial role in organisms and is susceptible to oxidative inactivation. Research has shown that PYROXD1 protects tRNA-LC from oxidative inactivation through a reducing mechanism.
Article
Multidisciplinary Sciences
Irma Querques, Michael Schmitz, Seraina Oberli, Christelle Chanez, Martin Jinek
Summary: This study reveals the molecular mechanism of RNA-guided target selection by Cas12k and the assembly of the TnsC filament in the CRISPR-associated transposon system. Cas12k primes TnsC polymerization and DNA remodelling for TnsB to catalyze site-specific transposon insertion, providing insights for the development of programmable site-specific gene insertion tools.
Article
Biology
Alena Kroupova, Fabian Ackle, Igor Asanovic, Stefan Weitzer, Franziska M. Boneberg, Marco Faini, Alexander Leitner, Alessia Chui, Ruedi Aebersold, Javier Martinez, Martin Jinek
Summary: RtcB enzymes are RNA ligases that are essential for various cellular processes, including tRNA splicing and RNA repair. In metazoa, RtcB functions as part of a larger tRNA ligase complex, with different subunits playing crucial roles in maintaining complex integrity. The crystal structures of key subunits provide insights into the catalytic mechanism and molecular architecture of the human tRNA ligase complex, shedding light on its functions in cellular RNA metabolism.
Article
Biochemistry & Molecular Biology
Martin Pacesa, Chun-Han Lin, Antoine Clery, Aakash Saha, Pablo R. Arantes, Katja Bargsten, Matthew J. Irby, Frederic H. -T. Allain, Giulia Palermo, Peter Cameron, Paul D. Donohoue, Martin Jinek
Summary: The crystallographic structures of Cas9 bound to off-target substrates reveal that noncanonical base-pairing interactions within the guide:off-target heteroduplex enable off-target binding. Single-nucleotide deletions in off-target substrates are accommodated by base skipping or multiple noncanonical base pairs. PAM-distal mismatches result in duplex unpairing and induce a conformational change in the Cas9 REC lobe. These insights contribute to the improved rational design of guide RNAs and off-target prediction algorithms.
Article
Multidisciplinary Sciences
Martin Pacesa, Luuk Loeff, Irma Querques, Lena M. Muckenfuss, Marta Sawicka, Martin Jinek
Summary: Researchers have used cryo-electron microscopy to observe the structural changes that occur during the binding and activation of Cas9. These findings provide a valuable structural framework for understanding the conformational checkpoint mechanism of Cas9 and may guide the development of new Cas9 variants and guide RNA designs with enhanced specificity and activity.
Article
Biology
Lena Maria Muckenfuss, Anabel Carmen Migenda Herranz, Franziska Maria Boneberg, Marcello Clerici, Martin Jinek
Summary: This study reports the interactions of human Fip1 with CPSF30 and CstF77, and demonstrates that CPSF contains two copies of hFip1 that increase the processivity of RNA polyadenylation by recruiting one copy of PAP. The study further reveals that the interaction between hFip1 and CstF77 is mediated via a short motif in the N-terminal acidic region of hFip1, and CstF77 competitively inhibits CPSF-dependent PAP recruitment and 3' polyadenylation.
Article
Chemistry, Physical
Lukasz Nierzwicki, Kyle W. East, Jonas M. Binz, Rohaine V. Hsu, Mohd Ahsan, Pablo R. Arantes, Erin Skeens, Martin Pacesa, Martin Jinek, George P. Lisi, Giulia Palermo
Summary: This study investigates the catalytic mechanism of CRISPR-Cas9 genome editing technology, revealing the relationship between active HNH nuclease and catalytic Mg2+ as well as the roles of catalytic residues H840 and K866. The findings provide valuable insights for enhancing the enzymatic function of CRISPR-Cas9.
Article
Biochemistry & Molecular Biology
Michael Schmitz, Irma Querques, Seraina Oberli, Christelle Chanez, Martin Jinek
Summary: This study uncovers the key mechanistic aspects underlying RNA-mediated assembly of CRISPR-associated transposons and their development as programmable tools for site-specific insertion of large DNA payloads.
Correction
Multidisciplinary Sciences
Martin Pacesa, Luuk Loeff, Irma Querques, Lena M. Muckenfuss, Marta Sawicka, Martin Jinek
Article
Biochemistry & Molecular Biology
Lukas Schmidheini, Nicolas Mathis, Kim Fabiano Marquart, Tanja Rothgangl, Lucas Kissling, Desiree Bock, Christelle Chanez, Jingrui Priscilla Wang, Martin Jinek, Gerald Schwank
Summary: CRISPR-Cas9 genome engineering is a powerful technology for correcting genetic diseases. In this study, researchers used phage-assisted continuous directed evolution to expand the PAM compatibility of CjCas9, resulting in a new variant called evoCjCas9. This variant can recognize a broader range of PAM sequences and has higher nuclease activity.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kenny Jungfer, Annina Sigg, Martin Jinek
Summary: This study reveals the structure and mechanism of the Thermoanaerobacter brockii Can2 enzyme in type III CRISPR-Cas immunity. The enzyme exhibits selective activity against single-stranded DNA and RNA, and achieves substrate specificity for CA dinucleotides through specific binding sites and molecular interactions. Furthermore, a molecular interaction relay between the cA4 binding site and the nuclease catalytic site is identified, enabling catalytic activation. These findings provide important insights into the function and applications of Can2 nucleases.
NUCLEIC ACIDS RESEARCH
(2023)
Meeting Abstract
Biotechnology & Applied Microbiology
Paul Donohoue, Martin Pacesa, Elaine Lau, Bastien Vidal, Matthew Irby, David Nyer, Tomer Rotstein, Lynda Banh, Mckenzi Toh, Jason Gibson, Bryan Kohrs, Kevin Baek, Arthur Owen, Euan Slorach, Megan van Overbeek, Chris Fuller, Andy May, Martin Jinek, Peter Cameron
Meeting Abstract
Biophysics
Kristina Makasheva, Louise Bryan, Martin Jinek, Beat Fierz
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Aakash Saha, Pablo R. Arantes, Mohd Ahsan, Martin Jinek, Giulia Palermo
BIOPHYSICAL JOURNAL
(2022)