Article
Biochemistry & Molecular Biology
Oran Melanker, Pierre Goloubinoff, Gideon Schreiber
Summary: In this study, directed in vitro evolution was used to select Uracil glycosylase (eUNG) variants that bind to different chaperones. The results showed that the different chaperones selected eUNG mutants with distinct mutation characteristics. GroEL was more effective in eliminating misfolded protein mutants, while DnaKJ selected mutants that were more likely to refold.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biophysics
Jiajun Lu, Xiaoyi Zhang, Yichao Wu, Yuebiao Sheng, Wenfei Li, Wei Wang
Summary: Through molecular simulations, it was discovered that Hsp70 maintains contact with substrate proteins during the folding process, shielding vulnerable sites to prevent misfolding and increasing folding efficiency. This suggests that in addition to its previously known functions, Hsp70 can facilitate folding by remodeling the energy landscape and directing the folding process, demonstrating a foldase scenario. These findings provide new insights into the molecular mechanisms of chaperone-mediated protein folding.
BIOPHYSICAL JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Zaida L. Almeida, Rui M. M. Brito
Summary: Protein aggregation and the formation of insoluble amyloid fibrils are intrinsic characteristics of amyloid diseases. Soluble oligomeric species formed during amyloid formation are highly cytotoxic and can lead to cell death and organ dysfunction. Disassembling preformed amyloids is a potential therapeutic strategy to arrest the progression of organ deterioration in amyloidosis. In this review, various chemical and biochemical agents capable of disaggregating amyloids are discussed, including their mode of action, structure, interactions with fibrillar structures, toxicity, and potential as treatment options.
Article
Biochemistry & Molecular Biology
Aleksandra A. Mamchur, Andrei Moiseenko, Irina S. Panina, Igor A. Yaroshevich, Sofia S. Kudryavtseva, Evgeny B. Pichkur, Olga S. Sokolova, Vladimir Muronetz, Tatiana B. Stanishneva-Konovalova
Summary: The study investigates the molecular interactions in the GroEL-PrP complex using cryo-EM and molecular dynamics approaches. It reveals that the N-domain of PrP forms more intermolecular contacts with GroEL, leading to the formation of short helices upon binding. Additionally, the C-domain of PrP tends to unfold its alpha 2-helix in the presence of GroEL.
Review
Cell Biology
Selin Altinok, Rebekah Sanchez-Hodge, Mariah Stewart, Kaitlan Smith, Jonathan C. Schisler
Summary: Heat shock proteins (HSPs) are a crucial family of molecular chaperones that play a vital role in maintaining protein homeostasis by regulating protein refolding and triage decisions. Interactions between HSPs and co-chaperone proteins can impact various cellular functions, with dysfunctions in this machinery potentially contributing to a range of human diseases. Therapeutic targeting of co-chaperones is being explored as a precise treatment approach for diseases related to protein quality control defects, although challenges remain due to the broad functions of HSPs.
Article
Multidisciplinary Sciences
Jonathan J. Knowlton, Daniel Gestaut, Boxue Ma, Gwen Taylor, Alpay Burak Seven, Alexander Leitner, Gregory J. Wilson, Sreejesh Shanker, Nathan A. Yates, B. V. Venkataram Prasad, Ruedi Aebersold, Wah Chiu, Judith Frydman, Terence S. Dermody
Summary: The TRiC chaperonin plays a crucial role in folding and assembly of the reovirus sigma 3 capsid protein, interacting with a network of chaperones including prefoldin. This study sheds light on the molecular dynamics of sigma 3 folding and establishes a biological function for TRiC in virus assembly, while also providing structural and functional insights into how TRiC and prefoldin participate in protein complex assembly.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Deepa Kumari, Jeffrey L. Brodsky
Summary: Protein quality control processes are crucial for cellular and organism health, particularly for polypeptides entering the endoplasmic reticulum (ER). ER-associated degradation (ERAD) is a multi-step pathway that targets inefficiently matured proteins for degradation, providing a mechanism to regulate protein levels and activities in the ER.
Article
Multidisciplinary Sciences
Il-Soo Park, Seongchan Kim, Yeajee Yim, Ginam Park, Jinahn Choi, Cheolhee Won, Dal-Hee Min
Summary: This study reports the creation of a synthetic chaperone to control the folding of therapeutic peptides and demonstrates its enhanced therapeutic potential in a tumor model. The synthetic chaperone, based on porous nanoparticles, provides an internal hydrophobic environment which stabilizes the secondary structure of the encapsulated peptides. Additionally, the modified nanoparticles serve as a nanoreactor and effectively deliver the stabilized peptides into cancer cells, resulting in inhibition of cancer growth.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Marco Janoschke, Mirjam Zimmermann, Anna Brunauer, Raffael Humbel, Tina Junne, Martin Spiess
Summary: The topology of membrane proteins is defined by the integration of alpha-helical transmembrane domains at the Sec61 translocon. Different sequences preceding a potential transmembrane domain significantly affect the hydrophobicity requirement for integration, with rapidly folding domains and strong chaperone binding facilitating efficient transmembrane integration.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Feihe Ma, Xiaohui Wu, Ang Li, Linlin Xu, Yingli An, Linqi Shi
Summary: The study revealed that the balance between capturing and releasing client proteins by nanochaperones plays a crucial role in regulating protein refolding. These findings could be applied to enzymes with different physicochemical properties, enabling efficient recovery of enzyme activity after storage or heating. This study provides new design strategies for nanochaperone systems to enhance their properties and applications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Lei Wan, Xi Chen, Wolfhard Almers
Summary: Syntaxin plays a crucial role in catalyzing membrane fusion during exocytosis and forms clusters in the plasma membrane. The mechanism of cluster formation differs between on-granule and off-granule clusters in live PC12 cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Lukas Rohland, Roman Kityk, Luka Smalinskaite, Matthias P. Mayer
Summary: The 70 kDa heat shock proteins (Hsp70s) are versatile molecular chaperones that assist in protein-folding processes. ATP and cochaperones induce structural rearrangements in Hsp70, with peptides causing larger changes and protein clients being more effective in stimulating ATP hydrolysis. The study provides insights into the mechanics, allostery, and dynamics of Hsp70 chaperones.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Anna Harari, Guy Zoltsman, Tal Levin, Rina Rosenzweig
Summary: This study structurally characterizes the interaction between Hsp104 NTD and substrates by using NMR spectroscopy. The NTD has a substrate-binding groove that specifically recognizes exposed hydrophobic stretches in Hsp104 substrates. The NTD itself also has chaperoning activities to protect the substrates from further misfolding and aggregation.
Article
Biochemistry & Molecular Biology
Alice Triveri, Carlos Sanchez-Martin, Luca Torielli, Stefano A. Serapian, Filippo Marchetti, Giovanni D'Acerno, Valentina Pirota, Matteo Castelli, Elisabetta Moroni, Mariarosaria Ferraro, Paolo Quadrelli, Andrea Rasola, Giorgio Colombo
Summary: In this study, the allosteric inhibition of the mitochondrial chaperone TRAP1 by a small molecule ligand is examined. The findings are used to design novel derivatives with interesting biological properties. The implications of this approach in understanding molecular regulation and designing allosteric small molecule modulators are discussed.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Medicinal
Sanket J. Mishra, Weiya Liu, Kristin Beebe, Monimoy Banerjee, Caitlin N. Kent, Vitumbiko Munthali, John Koren, John A. Taylor, Leonard M. Neckers, Jeffrey Holzbeierlein, Brian S. J. Blagg
Summary: Hsp90 proteins play a crucial role in cancer progression, and inhibiting their activity may be beneficial for cancer treatment. Current Hsp90 inhibitors target all isoforms, potentially leading to adverse effects. Utilizing Hsp90 beta-selective inhibitors as a new approach for cancer therapy holds promise in reducing side effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Plant Sciences
Kathrin Kowarschik, Wolfgang Hoehenwarter, Sylvestre Marillonnet, Marco Trujillo
Article
Plant Sciences
Yanmei Chen, Wolfgang Hoehenwarter
Article
Biochemistry & Molecular Biology
Tobias Hedtke, Christoph U. Schraeder, Andrea Heinz, Wolfgang Hoehenwarter, Jurgen Brinckmann, Thomas Groth, Christian E. H. Schmelzer
Article
Biochemistry & Molecular Biology
Alena Soboleva, Gregory Mavropulo-Stolyarenko, Tatiana Karonova, Domenika Thieme, Wolfgang Hoehenwarter, Christian Ihling, Vasily Stefanov, Tatiana Grishina, Andrej Frolov
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Plant Sciences
Naheed Tabassum, Lennart Eschen-Lippold, Benedikt Athmer, Manaswita Baruah, Martina Brode, Luis D. Maldonado-Bonilla, Wolfgang Hoehenwarter, Gerd Hause, Dierk Scheel, Justin Lee
Article
Biochemistry & Molecular Biology
Preety Panwar, Tobias Hedtke, Andrea Heinz, Pierre-Marie Andrault, Wolfgang Hoehenwarter, David J. Granville, Christian E. H. Schmelzer, Dieter Bromme
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2020)
Article
Multidisciplinary Sciences
Michael Niemeyer, Elena Moreno Castillo, Christian H. Ihling, Claudio Iacobucci, Verona Wilde, Antje Hellmuth, Wolfgang Hoehenwarter, Sophia L. Samodelov, Matias D. Zurbriggen, Panagiotis L. Kastritis, Andrea Sinz, Luz Irina A. Calderon Villalobos
NATURE COMMUNICATIONS
(2020)
Article
Plant Sciences
Anja Roediger, Johann Galonska, Elena Bergner, Birgit Agne, Stefan Helm, Saleh Alseekh, Alisdair R. Fernie, Domenika Thieme, Wolfgang Hoehenwarter, Gerd Hause, Thomas Pfannschmidt, Sacha Baginsky
Article
Plant Sciences
Xiyuan Jiang, Wolfgang Hoehenwarter, Dierk Scheel, Justin Lee
Article
Biochemistry & Molecular Biology
Mona Bassal, Mohammad Abukhalaf, Petra Majovsky, Domenika Thieme, Tobias Herr, Mohamed Ayash, Naheed Tabassum, M. H. D. Rami Al Shweiki, Carsten Proksch, Ali Hmedat, Joerg Ziegler, Justin Lee, Steffen Neumann, Wolfgang Hoehenwarter
Review
Biochemistry & Molecular Biology
Galina Smolikova, Daria Gorbach, Elena Lukasheva, Gregory Mavropolo-Stolyarenko, Tatiana Bilova, Alena Soboleva, Alexander Tsarev, Ekaterina Romanovskaya, Ekaterina Podolskaya, Vladimir Zhukov, Igor Tikhonovich, Sergei Medvedev, Wolfgang Hoehenwarter, Andrej Frolov
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Correction
Multidisciplinary Sciences
Michael Niemeyer, Elena Moreno Castillo, Christian H. Ihling, Claudio Iacobucci, Verona Wilde, Antje Hellmuth, Wolfgang Hoehenwarter, Sophia L. Samodelov, Matias D. Zurbriggen, Panagiotis L. Kastritis, Andrea Sinz, Luz Irina A. Calderon Villalobos
NATURE COMMUNICATIONS
(2021)
Article
Biology
Pascal Puellmann, Anja Knorrscheidt, Judith Muench, Paul R. Palme, Wolfgang Hoehenwarter, Sylvestre Marillonnet, Miguel Alcalde, Bernhard Westermann, Martin J. Weissenborn
Summary: Pullmann et al developed a modular Golden Gate-based secretion system, enabling production and one-step purification of active fungal unspecific peroxygenases (UPOs) in yeast. Their system was applied to enantioselective conversion on a preparative scale, demonstrating the potential for future use in other genes of interest suitable for production in yeast.
COMMUNICATIONS BIOLOGY
(2021)
Article
Plant Sciences
Mohamed Ayash, Mohammad Abukhalaf, Domenika Thieme, Carsten Proksch, Mareike Heilmann, Martin Hartmut Schattat, Wolfgang Hoehenwarter
Summary: The plant nucleus, despite its importance in genetic information and gene expression, has been understudied. In this study, nuclear proteome fractions from Arabidopsis thaliana cells treated with two elicitors of plant immunity were analyzed. The research revealed potential nuclear protein import upon elicitation of immunity and changes in protein abundance in the nucleus related to plant immunity processes. Promiscuous ribosome assembly and the role of prohibitins and cytochrome C in plant immune responses were also highlighted.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Carla Brillada, Ooi-Kock Teh, Franck Anicet Ditengou, Chil-Woo Lee, Till Klecker, Bushra Saeed, Giulia Furlan, Marco Zietz, Gerd Hause, Lennart Eschen-Lippold, Wolfgang Hoehenwarter, Justin Lee, Thomas Ott, Marco Trujillo
Summary: Exo70B2 acts as a subunit of the exocyst in the immune response pathway and is involved in regulating transport into vacuoles through interactions with ATG8 and dependence on autophagy. Phosphorylation of Exo70B2 affects its localization and interaction with ATG8, ultimately impacting effector-triggered immunity and sensitivity to BTH. This study provides insights into the molecular mechanisms that divert Exo70B2 from secretion to autophagy for degradation in order to modulate secretory activity during immune responses.