Article
Multidisciplinary Sciences
Maximilian M. Biebl, Abraham Lopez, Alexandra Rehn, Lee Freiburger, Jannis Lawatscheck, Birgit Blank, Michael Sattler, Johannes Buchner
Summary: The study shows that a tryptophan residue in the proximal region of the p23 tail decelerates the ATPase of Hsp90 by altering the conformation of the catalytic loop, while a conserved helical motif in the p23 tail interacts with the client protein binding site of Hsp90 and is involved in the activation of the client protein in the cellular context.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Siddhi Omkar, Tasaduq H. Wani, Bo Zheng, Megan M. Mitchem, Andrew W. Truman
Summary: This study shows that APE2 and Apn2 proteins depend on the chaperone system in yeast and mammalian cells, and suggests that inhibiting chaperones may be a potential anticancer therapy targeting APE2-mediated processes.
Article
Biochemistry & Molecular Biology
Maria Dauden, Andres Lopez-Perrote, Oscar Llorca
Summary: RUVBL1 and RUVBL2 are highly conserved AAA+ ATPases that form a hetero-hexameric complex involved in various cellular processes. Recent cryo-EM studies have provided insights into their role in complex protein-protein interactions.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Chemistry, Analytical
Helisa H. Wippel, Juan D. Chavez, Andrew D. Keller, James E. Bruce
Summary: The XL-MS technique provides insight into protein conformations and interactions within their cellular environment, while the iqPIR strategy allows for comparative interactome studies using isotope encoded chemical cross-linkers. Multiplexed iqPIR enables quantitative interactome analysis of up to six biological samples in a single LC-MS acquisition, revealing specific protein conformational and interaction changes in response to different inhibitors.
ANALYTICAL CHEMISTRY
(2022)
Article
Plant Sciences
Larissa Machado Antonio, Gustavo Henrique Martins, Annelize Zambon Barbosa Aragao, Natalia Galdi Quel, Gabriel Zazeri, Walid A. Houry, Carlos Henrique Inacio Ramos
Summary: The chaperone R2TP plays an important role in protein assembly and its study in plant systems provides valuable insights. The protein RPAP3 in Sorghum bicolor has been identified and shown to have similar functions as its counterparts in yeast and humans. Understanding the role of RPAP3 in plant R2TP complex can contribute to advancements in plant biology and biotechnological applications.
Article
Biochemistry & Molecular Biology
Taylor Arhar, Arielle Shkedi, Cory M. Nadel, Jason E. Gestwicki
Summary: Molecular chaperones, despite their diverse sequences, sizes, and shapes, all bind to unfolded proteins to assist in their folding. Recent advancements in NMR spectroscopy have allowed for detailed studies on how different chaperones interact with client proteins. These studies have revealed both similarities and differences in how chaperones release clients and how ATP cycling affects the folding process.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Yu-Ying Chen, Thomas V. O'Halloran
Summary: Zinc is crucial for living organisms, and it has been discovered that the ZNG1 family of GTPases function as metallochaperones, directly transferring zinc to and activating methionine aminopeptidases which play essential roles in protein modification during or after translation.
Review
Biochemistry & Molecular Biology
Anna G. Mankovich, Brian C. Freeman
Summary: Heat shock protein 90 (Hsp90), a highly conserved molecular chaperone, not only maintains the stability of metastable proteins, but also plays a crucial role in protein transport. The specific contributions of Hsp90 to protein transport are still not well defined, despite numerous connections with factors involved in this process.
Article
Biochemistry & Molecular Biology
Nicolas Bloemeke, Kevin Meighen-Berger, Manuel Hitzenberger, Nina C. Bach, Marina Parr, Joao Pl Coelho, Dmitrij Frishman, Martin Zacharias, Stephan A. Sieber, Matthias J. Feige
Summary: One-third of the human proteome is composed of membrane proteins, which are susceptible to misfolding and require folding assistance from chaperones. Calnexin, an abundant ER chaperone, interacts with a large number of membrane proteins, including misfolded ones, using its lectin domain and transmembrane domain for recognition and binding. This study reveals the widespread role of calnexin in recognizing client proteins in the lipid bilayer and highlights its importance in supporting membrane protein biogenesis.
Article
Chemistry, Multidisciplinary
Chuan-jing Cheng, Kai-xin Liu, Man Zhang, Fu-kui Shen, Li-li Ye, Wen-bo Wu, Xiao-tao Hou, Er-wei Hao, Yuan-yuan Hou, Gang Bai
Summary: This study identified a novel natural inhibitor of HSP90, okicamelliaside (OCS), which selectively inhibits the formation of the HSP90-CDC37 protein complex and disrupts protein-protein interactions of HSP90-CDC37 to exert anti-tumor effects.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Dennis M. Bjorklund, R. Marc L. Morgan, Jasmeen Oberoi, Katie L. I. M. Day, Panagiota A. Galliou, Chrisostomos Prodromou
Summary: The study identified the interaction between CDC37 and BRAF and determined the crucial structural elements of CDC37 involved in BRAF recognition. The dimerization of BRAF can inhibit the recognition by CDC37, and the consequences of BRAF mutations on signaling were discussed.
Article
Biochemistry & Molecular Biology
Thiago Seraphim, Nardin Nano, Yiu Wing Sunny Cheung, Siripat Aluksanasuwan, Carolina Colleti, Yu-Qian Mao, Vaibhav Bhandari, Gavin Young, Larissa Holl, Sadhna Phanse, Yuliya Gordiyenko, Daniel R. Southworth, Carol Robinson, Visith Thongboonkerd, Lisandra M. Gava, Julio C. Borges, Mohan Babu, Leandro R. S. Barbosa, Carlos H. Ramos, Philipp Kukura, Walid A. Houry
Summary: The R2TP complex, formed by RUVBL1 and RUVBL2 ATPases, associates with PIH1D1 and RPAP3 proteins and plays a role in promoting the formation of macromolecular complexes. RPAP3 is identified as the central subunit of R2TP, linking PIH1D1 and RUVBL1/2. The study provides insights into the structure and function of the R2TP complex.
Review
Biochemistry & Molecular Biology
Chrisostomos Prodromou, Dennis M. Bjorklund
Summary: Hsp90, an ATP molecular chaperone, plays a crucial role in the activation and maturation of client proteins. Recent studies have shed light on the mechanism of Hsp90, including its ATP hydrolysis and the remodeling of client proteins for their activation.
Article
Chemistry, Multidisciplinary
Nam Gu Yoon, Hakbong Lee, So-Yeon Kim, Sung Hu, Darong Kim, Sujae Yang, Ki Bum Hong, Ji Hoon Lee, Soosung Kang, Byung-Gyu Kim, Kyungjae Myung, Changwook Lee, Byoung Heon Kang
Summary: The study identified Mitoquinone (MitoQ) as a potent inhibitor of mitochondrial Hsp90, offering potential anticancer properties. By competitively binding with TRAP1 clients, MitoQ facilitated the identification of mitochondrial protein interactions. Targeting the client binding site of Hsp90 family proteins provides a novel strategy for developing potent anticancer drugs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Pharmacology & Pharmacy
Mina Ardestani, Zahra Khorsandi, Fariba Keshavarzipour, Siavash Iravani, Hojjat Sadeghi-Aliabadi, Rajender S. Varma
Summary: Heat shock proteins (Hsps) play important roles in cancer therapy, and Hsp90 inhibitors are attractive therapeutic agents that can inhibit tumor growth and development.
Article
Biochemistry & Molecular Biology
Antonio Galindo, Vicente J. Planelles-Herrero, Gianluca Degliesposti, Sean Munro
Summary: TRAPP complexes, which are nucleotide exchange factors, play vital roles in membrane traffic and autophagy. TRAPPII activates Rab11, while TRAPPIII activates Rab1, with shared core subunits affecting nucleotide exchange and specific large subunits essential for in vivo activity. Cryo-EM structures reveal the assembly of TRAPPIII complex, showing how TRAPPIII-specific subunits hold the catalytic core and large arms determine specificity. The lower resolution structure of TRAPPII suggests evolution from a single ur-TRAPP.
Article
Cell Biology
Mohinder Pal, Hugo Munoz-Hernandez, Dennis Bjorklund, Lihong Zhou, Gianluca Degliesposti, J. Mark Skehel, Emma L. Hesketh, Rebecca F. Thompson, Laurence H. Pearl, Oscar Llorca, Chrisostomos Prodromou
Summary: The R2TP complex, in collaboration with HSP90, functions as a chaperone for the assembly and stability of protein complexes, with the stability of PIKKs like TOR depending on the TTT complex. TTT regulates the R2TP chaperone by inhibiting RUVBL1-RUVBL2 ATPase activity and modulating the conformation and interactions of PIH1D1 and RPAP3 components.
Article
Biochemistry & Molecular Biology
Xabier Agirrezabala, Ekaterina Samatova, Meline Macher, Marija Liutkute, Manisankar Maiti, David Gil-Carton, Jiri Novacek, Mikel Valle, Marina Rodnina
Summary: Cellular proteins begin to fold as they emerge from the ribosome. The folding process is influenced by both the amino acid sequence and the interactions with the ribosome. Research shows that folding of a beta-barrel protein starts with the formation of a dynamic alpha-helix inside the ribosome, and the N-terminal part of the nascent chain refolds to a beta-hairpin structure before its release from the ribosome.
Article
Biochemistry & Molecular Biology
Marina Serna, Ana Gonzalez-Corpas, Sofia Cabezudo, Andres Lopez-Perrote, Gianluca Degliesposti, Eduardo Zarzuela, J. Mark Skehel, Javier Munoz, Oscar Llorca
Summary: This study reveals the role of ZNHIT2 in the regulation of R2TP chaperone during the biogenesis of PRPF8. ZNHIT2 forms a complex with R2TP and alters the conformation and nucleotide state of RUVBL1-RUVBL2, affecting its ATPase activity. PRPF8 interacts directly with R2TP and this complex can incorporate ZNHIT2 and other proteins involved in the biogenesis of PRPF8.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Chrisostomos Prodromou, Dennis M. Bjorklund
Summary: Hsp90, an ATP molecular chaperone, plays a crucial role in the activation and maturation of client proteins. Recent studies have shed light on the mechanism of Hsp90, including its ATP hydrolysis and the remodeling of client proteins for their activation.
Article
Biochemistry & Molecular Biology
Dennis M. Bjorklund, R. Marc L. Morgan, Jasmeen Oberoi, Katie L. I. M. Day, Panagiota A. Galliou, Chrisostomos Prodromou
Summary: The study identified the interaction between CDC37 and BRAF and determined the crucial structural elements of CDC37 involved in BRAF recognition. The dimerization of BRAF can inhibit the recognition by CDC37, and the consequences of BRAF mutations on signaling were discussed.
Article
Multidisciplinary Sciences
Jorge Pedro Lopez-Alonso, Melisa Lazaro, David Gil-Carton, Philip H. Choi, Liang Tong, Mikel Valle
Summary: This study investigates the structure of active pyruvate carboxylase tetramers using cryoEM and reveals the catalytic steps and substrate-product identification. The analysis of catalytically active PC tetramers uncovers the role of certain motions during enzyme functioning and the mechanism for allosteric regulation.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Yves U. Tittes, Dominik A. Herbst, Solene F. X. Martin, Hugo Munoz-Hernandez, Roman P. Jakob, Timm Maier
Summary: Polyketide synthases (PKSs) are microbial biosynthetic enzymes that can assemble potent bioactive natural products. The modular architecture of PKS assembly lines plays a crucial role in substrate transfer and enzyme sequestration.
Article
Biochemistry & Molecular Biology
Javier Coloma, Nayim Gonzalez-Rodriguez, Francisco A. Balaguer, Karolina Gmurczyk, Clara Aicart-Ramos, oscar M. Nuero, Juan Roman Luque-Ortega, Kimberly Calugaru, Neal F. Lue, Fernando Moreno-Herrero, Oscar Llorca
Summary: Cdc13 plays a crucial role in telomere replication and stability by forming dimers and higher-order complexes, which regulate binding and structure of DNA.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Angel Rivera-Calzada, Raquel Arribas-Bosacoma, Alba Ruiz-Ramos, Paloma Escudero-Bravo, Jasminka Boskovic, Rafael Fernandez-Leiro, Antony W. Oliver, Laurence H. Pearl, Oscar Llorca
Summary: Vaccinia virus uses proteins C4 and C16 to interfere with the host immune response. The authors provide the structural basis for this viral defense mechanism, which is conserved in other poxviruses.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Sara De Braganc, Clara Aicart-Ramos, Raquel Arribas-Bosacoma, Angel Rivera-Calzada, Juan Pablo Unfried, Laura Prats-Mari, Mikel Marin-Baquero, Puri Fortes, Oscar Llorca, Fernando Moreno-Herrero
Summary: The synapsis of DNA ends is a critical step for the repair of double-strand breaks by non-homologous end joining (NHEJ). In this study, the contributions of core NHEJ proteins and accessory factors APLF and lncRNA NIHCOLE to DNA synapsis were investigated using magnetic tweezers. APLF stabilizes DNA end bridging and, together with Ku70-Ku80, establishes a minimal complex that supports DNA synapsis. NIHCOLE increases the dwell time of the synapses by Ku70-Ku80 and APLF, and this effect is enhanced by a small structured RNA domain within NIHCOLE. A model is proposed where Ku70-Ku80 can bind DNA, APLF, and structured RNAs simultaneously to promote stable DNA end joining.
Article
Biochemistry & Molecular Biology
Carlos Lopez-Robles, Stefano Scaramuzza, Elsa N. Astorga-Simon, Morie Ishida, Chad D. Williamson, Soledad Banos-Mateos, David Gil-Carton, Miguel Romero-Durana, Ander Vidaurrazaga, Juan Fernandez-Recio, Adriana L. Rojas, Juan S. Bonifacino, Daniel Castano-Diez, Aitor Hierro
Summary: Using cryo-electron tomography, Lopez-Robles, Scaramuzza, Astorga-Simon, Ishida et al. solve the architecture of ESCPE-1, a protein scaffold that mediates the recycling of cargo from endosome to trans-Golgi network and plasma membrane in tubular carriers. The study reveals that ESCPE-1 has a single-layer coat organization and suggests that synergistic interactions between ESCPE-1 protomers, phosphoinositides, and cargo molecules drive tubule formation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Nuria Gallisa-Sune, Paula Sanchez-Fernandez-de-Landa, Fabian Zimmermann, Marina Serna, Laura Regue, Joel Paz, Oscar Llorca, Jens Luders, Joan Roig
Summary: This study demonstrates that the adaptor protein BICD2 is activated through phosphorylation, which promotes the formation of the dynein motor complex and regulates its localization and activity within cells. This finding is crucial for understanding the functional importance of dynein in both dividing and non-dividing cells.
NATURE COMMUNICATIONS
(2023)
Review
Genetics & Heredity
Alejandro Parra, Rachel Rabin, John Pappas, Patricia Pascual, Mario Cazalla, Pedro Arias, Natalia Gallego-Zazo, Alfredo Santana, Ignacio Arroyo, Merce Artigas, Harry Pachajoa, Yasemin Alanay, Ozlem Akgun-Dogan, Lyse Ruaud, Nathalie Couque, Jonathan Levy, Gloria Liliana Porras-Hurtado, Fernando Santos-Simarro, Maria Juliana Ballesta-Martinez, Encarna Guillen-Navarro, Hugo Munoz-Hernandez, Julian Nevado, Jair Tenorio-Castano, Pablo Lapunzina
Summary: SETD2 is a histone methyltransferase protein associated with three different disorders: Luscan-Lumish syndrome (LLS), intellectual developmental disorder, autosomal dominant 70 (MRD70), and Rabin-Pappas syndrome (RAPAS). These disorders have distinct clinical and molecular features, including overgrowth, intellectual disability, speech delay, and dysmorphic facial features. Variants in the SETD2 gene can cause these disorders, and this article reports on 18 new patients with SETD2 variants and reviews 33 previously reported patients. The article expands our understanding of the clinical features and similarities and differences among these three disorders.
Editorial Material
Biochemistry & Molecular Biology
Chrisostomos Prodromou
