Article
Biochemistry & Molecular Biology
Ahmad Aljohmani, Bastian Opitz, Markus Bischoff, Daniela Yildiz
Summary: This study found that infection with Pseudomonas aeruginosa and Streptococcus pneumoniae stimulates the activation of ADAM10 in epithelial cells, leading to inflammatory cell recruitment and loss of barrier integrity. The activation is based on the toxin repertoire rather than the bacterial particle itself.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Rolake O. Alabi, Jose Lora, Arda B. Celen, Thorsten Maretzky, Carl P. Blobel
Summary: The Notch signaling pathway relies on the roles of proteins like ADAM10 and ADAM17 to regulate cell fate, with ADAM17 preferring to process Notch1 in ligand-independent conditions, and ADAM10 preferring to process Notch1 in ligand-dependent conditions. These findings provide new insights into the substrate selectivity mechanisms of ADAM10 and ADAM17 towards Notch1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ludwig Werny, Antonia Grogro, Kira Bickenbach, Cynthia Bulck, Fred Armbrust, Tomas Koudelka, Kriti Pathak, Franka Scharfenberg, Martin Sammel, Farah Sheikhouny, Andreas Tholey, Stefan Linder, Christoph Becker-Pauly
Summary: This study investigated the interaction between membrane-type-I matrix metalloproteinase (MT1-MMP) and meprin beta, revealing a potential regulatory connection between the two enzymes.
Review
Biochemistry & Molecular Biology
Neale Harrison, Chek Ziu Koo, Michael G. Tomlinson
Summary: ADAM10 acts as a molecular scissor by cleaving membrane protein substrates through ectodomain shedding, interacting with various substrates and particularly with the TspanC8 subgroup of tetraspanins. Recent studies suggest that different TspanC8/ADAM10 complexes have distinct substrates, offering therapeutic potential for diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Khuram U. Ashraf, Rie Nygaard, Owen N. Vickery, Satchal K. Erramilli, Carmen M. Herrera, Thomas H. McConville, Vasileios I. Petrou, Sabrina I. Giacometti, Meagan Belcher Dufrisne, Kamil Nosol, Allen P. Zinkle, Chris L. B. Graham, Michael Loukeris, Brian Kloss, Karolina Skorupinska-Tudek, Ewa Swiezewska, David I. Roper, Oliver B. Clarke, Anne-Catrin Uhlemann, Anthony A. Kossiakoff, M. Stephen Trent, Phillip J. Stansfeld, Filippo Mancia
Summary: This study presents the structures of WaaL from Cupriavidus metallidurans and provides molecular details and a mechanistic model for lipopolysaccharide maturation.
Article
Biology
Kangcheng Song, Miao Wei, Wenjun Guo, Li Quan, Yunlu Kang, Jing-Xiang Wu, Lei Chen
Summary: TRPC5 channel is a nonselective cation channel involved in various physiological processes. Inhibitors of TRPC5, such as clemizole and HC-070, stabilize the ion channel in a nonconductive closed state, potentially offering new therapeutic strategies for anxiety disorders, depression, and kidney diseases. The cryo-EM structures of human TRPC5 with inhibitors provide insights into the binding sites and inhibitory mechanisms, facilitating the development of more effective inhibitors targeting TRPC5.
Article
Biochemistry & Molecular Biology
Lisa Hitschler, Thorsten Lang
Summary: Neurotoxic amyloid 11-peptides are believed to contribute to Alzheimer's disease, and this study investigates the physical interactions between amyloid precursor protein (APP) and alpha-secretases. It is found that the transmembrane domain of APP is required for association with alpha-secretases and is involved in alpha-processing, suggesting the dominant role of ADAM10 in APP cleavage. Further understanding of this interaction may aid in the development of therapeutic strategies for Alzheimer's disease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Qin Gong, Kim Robinson, Chenrui Xu, Phuong Thao Huynh, Kelvin Han Chung Chong, Eddie Yong Jun Tan, Jiawen Zhang, Zhao Zhi Boo, Daniel Eng Thiam Teo, Kenneth Lay, Yaming Zhang, John Soon Yew Lim, Wah Ing Goh, Graham Wright, Franklin L. Zhong, Bruno Reversade, Bin Wu
Summary: NLRP1 and CARD8 are two recently characterized sensor proteins for the human inflammasome complex. The cryo-EM CARD filament structures of the NLRP1 and CARD8 activating domains reveal how NLRP1 and CARD8 discriminate between ASC and pro-caspase-1. The authors propose a two-step model for NLRP1 activation.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jialiang Wang, Jingdan Liang, Lu Chen, Wei Zhang, Liangliang Kong, Chao Peng, Chen Su, Yi Tang, Zixin Deng, Zhijun Wang
Summary: Statins, effective cholesterol-lowering drugs, depend on a megasynthase complex for biosynthesis. CryoEM structures of LovB-LovC and core LovB provide insights into the catalytic cycle for lovastatin production.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Amy M. Weeks
Summary: Phosphorylation within caspase cleavage sites can affect the efficiency of substrate cleavage by attenuating the rate, but inhibition can sometimes be overcome by additional favorable substrate features, suggesting nuanced physiological roles for phosphorylation of caspase substrates. These findings have implications for targeting caspases with chemical probes and therapeutics.
BIOCHEMICAL JOURNAL
(2021)
Review
Chemistry, Multidisciplinary
Helen Zgurskaya, John K. Walker, Jerry M. Parks, Valentin V. Rybenkov
Summary: Antibiotics are effective against infectious bacterial diseases, but antibiotic-resistant bacteria present a challenge to modern medicine. Gram-negative bacteria, with their outer membrane acting as a permeability barrier, rely on active efflux and low permeability to resist antibiotics. Efforts to overcome this resistance include enhancing antibiotic penetration and inhibiting efflux pumps, offering potential for novel therapeutic strategies.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Julio Abril-Garrido, Christian Dienemann, Frauke Grabbe, Taras Velychko, Michael Lidschreiber, Haibo Wang, Patrick Cramer
Summary: At active human genes, the +1 nucleosome is located downstream of the RNA polymerase II pre-initiation complex. Inactive genes have the +1 nucleosome positioned further upstream, at a promoter-proximal location. A model system shows that a promoter-proximal +1 nucleosome can inhibit RNA synthesis, and this is attributed to the structural basis of the pre-initiation complex. The position of the nucleosome edge relative to the transcription start site determines the assembly and activity of the pre-initiation complex, with a closer proximity resulting in inhibition.
Article
Multidisciplinary Sciences
Nadja Leinung, Torben Mentrup, Mehul Patel, Tom Gallagher, Bernd Schroeder
Summary: SPPL2a/b proteases interact with tetraspanins, facilitating protease-substrate encounters within the cell membrane. These findings contribute to our understanding of protease-substrate interactions and support the role of tetraspanins in membrane-embedded proteolytic processes.
Article
Multidisciplinary Sciences
Yiwei Chen, Kai Xu, Luca Piccoli, Mathilde Foglierini, Joshua Tan, Wenjie Jin, Jason Gorman, Yaroslav Tsybovsky, Baoshan Zhang, Boubacar Traore, Chiara Silacci-Fregni, Claudia Daubenberger, Peter D. Crompton, Roger Geiger, Federica Sallusto, Peter D. Kwong, Antonio Lanzavecchia
Summary: This study demonstrates that Plasmodium falciparum RIFINs can bind to LILRB1 through D3, and inserting receptor domains into the VH-CH1 elbow can generate novel antibodies, as shown by a naturally selected example.
Article
Chemistry, Physical
Jose-Luis Velasco-Bolom, Laura Dominguez
Summary: The study utilizing molecular dynamics simulations and network analysis revealed the dynamic behavior of γ-secretase in its apo form and bound to different substrates, highlighting the crucial role of the NCT-lobule in communication and dynamics. Systems with long extracellular substrates, such as APP-C99 and Notch, preferred compact conformations.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)