Article
Multidisciplinary Sciences
Bin Huang, Ming Sun, Reyal Hoxie, Judy L. M. Kotler, Larry J. Friedman, Jeff Gelles, Timothy O. Street
Summary: Hsp70 and Hsp90 chaperones play important roles in protein quality control. This study reveals that BiP, a Hsp70 chaperone, acts as a cochaperone to accelerate the closure of Grp94, a Hsp90 chaperone. BiP achieves this by interacting with the middle domain of Grp94. These findings provide insights into the enhanced activity of BiP and Grp94 when working together.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Erin E. Deans, Judy L. M. Kotler, Wei-Shao Wei, Timothy O. Street
Summary: This study investigates the interaction between Hsp70 chaperones and client protein proIGF2, revealing that electrostatic attraction plays a crucial role in facilitating the recognition of oligomers.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Endocrinology & Metabolism
Balamurugan Dhayalan, Deepak Chatterjee, Yen-Shan Chen, Michael A. Weiss
Summary: Analysis of diabetes-associated mutations in the human insulin gene has provided insights into the folding mechanisms of proinsulin, revealing the impact of mutations on pancreatic beta-cell dysfunction and insulin secretion. Studies suggest that conserved residues play a crucial role in folding efficiency and the susceptibility of proinsulin to impaired foldability can contribute to the development of diseases. This highlights the molecular links between biophysical principles and the impact on diseases such as diabetes and obesity.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Paola Turina, Piero Fariselli, Emidio Capriotti
Summary: The study of protein folding is crucial for understanding protein function and the relationship between genetics and phenotypes. K-Pro is a new database that collects experimental kinetic data on monomeric proteins with a two-state folding mechanism. It provides a user-friendly interface for browsing and downloading relevant data.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
R. Charlotte Eccleston, David D. Pollock, Richard A. Goldstein
Summary: Epistasis and cooperativity in protein folding are both influenced by networks of energetic interactions within proteins, and their selection can affect each other. Selection for cooperativity may be crucial for predicting protein structure using epistasis measurements.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Tae-Eun Kim, Kotaro Tsuboyama, Scott Houliston, Cydney M. Martell, Claire M. Phoumyvong, Alexander Lemak, Hugh K. Haddox, Cheryl H. Arrowsmith, Gabriel J. Rocklin
Summary: Designing new protein structures remains challenging, and our study successfully designed stable aPPa proteins through large-scale design and test cycles, shedding light on the biophysical determinants of folding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Rafayel Petrosyan, Abhishek Narayan, Michael T. Woodside
Summary: Single-molecule force spectroscopy (SMFS) is a powerful tool for studying protein folding dynamics, uncovering energy landscapes of folding, complex folding pathways, mechanisms of chaperones in assisting folding, effects of ribosomes on co-translational folding, and monitoring membrane protein folding.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Irina Sorokina, Arcady R. Mushegian, Eugene V. Koonin
Summary: The prevailing thermodynamic hypothesis of protein folding is called into question due to the lack of strong empirical evidence. Physical theory-based approaches in predicting protein folds have largely failed, except for small proteins. Recent successes in protein structure prediction have been achieved through evolutionary modeling and deep learning methods, but provide no insights into protein folding mechanisms and pathways. An alternative view suggests that most proteins do not occupy the global minimum of free energy, but instead a local minimum on a fluctuating landscape. This view also argues that the majority of proteins require energy-dependent cellular processes for folding, such as interactions with the translation system and chaperones.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Pavlo Potalitsyn, Lucie Mrazkova, Irena Selicharova, Michaela Tencerova, Michaela Ferencakova, Martina Chrudinova, Tereza Turnovska, Andrzej Marek Brzozowski, Ales Marek, Jakub Kaminsky, Jiri Jiracek, Lenka Zakova
Summary: Insulin-like Growth Factor-2 (IGF2) is essential for human embryonic growth, development, and adult physiology. The incorrect processing of the IGF2 precursor results in the formation of two proforms, big-IGF2(87) and big-IGF2(104). These proforms, especially pro-IGF2(156) and big-IGF2(104), may be associated with diseases related to the high levels of IGF-2 proforms in the bloodstream.
COMMUNICATIONS BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Awa Diop, Daniele Santorelli, Francesca Malagrino, Caterina Nardella, Valeria Pennacchietti, Livia Pagano, Lucia Marcocci, Paola Pietrangeli, Stefano Gianni, Angelo Toto
Summary: This review summarizes the latest research on the structure, function, pathogenic role, and regulation of SH2 domains. The findings suggest that pharmacological interest in SH2 domains and a deeper understanding of their binding properties are crucial.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Cameron Wells, Samuel Brennan, Matt Keon, Lezanne Ooi
Summary: Neurodegenerative diseases such as AD, PD, HD, and ALS are rooted in the activities of amyloid-like proteins, with monomeric proteins undergoing conformational shifts to facilitate aggregation and formation of solid fibrils. Oligomeric stages are key drivers of neuronal toxicity, and feedback within the pathway results in exponential acceleration of aggregation. The complex protein dynamics contribute to the late onset and accelerating progression of these disorders, affecting cellular interactions and environment. Targeting core elements of pathological progression may hold promise for future therapies.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Neurosciences
Carlos Costas-Insua, Estefania Moreno, Irene B. Maroto, Andrea Ruiz-Calvo, Raquel Bajo-Graneras, David Martin-Gutierrez, Rebeca Diez-Alarcia, M. Teresa Vilaro, Roser Cortes, Nuria Garcia-Font, Ricardo Martin, Marc Espina, Joaquin Botta, Silvia Gines, Peter J. McCormick, Jose Sanchez-Prieto, Ismael Galve-Roperh, Guadalupe Mengod, Leyre Uriguen, Giovanni Marsicano, Luigi Bellocchio, Enric Canela, Vicent Casado, Ignacio Rodriguez-Crespo, Manuel Guzman
Summary: The study identified BiP as a protein interacting with CB1R to modulate the effects of cannabinoids in the brain, showing a selective impact on signaling pathways and neuron types.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Louise Laursen, Stefano Gianni, Per Jemth
Summary: This study investigates the folding of a three-domain supramodule from the protein PSD-95, revealing that the PDZ domain folds faster and independently from the SH3-GK tandem. However, concurrent folding of the PDZ domain slows down folding of SH3-GK, resulting in an off-pathway folding intermediate. This contributes to the understanding of multidomain protein folding where individual domains cannot be viewed as separate folding units.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Leonore Novak, Maria Petrosino, Daniele Santorelli, Roberta Chiaraluce, Valerio Consalvi, Alessandra Pasquo, Carlo Travaglini-Allocatelli
Summary: A Phi value analysis was conducted on BRD2(2) to investigate its folding pathway, revealing that the C-terminal region serves as the initial folding nucleus, with the N-terminal region consolidating its structure later in the process. This indicates a hierarchical mechanism of protein folding with non-native interactions playing a significant role.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Irena Roterman, Katarzyna Stapor, Leszek Konieczny
Summary: The protein folding process is influenced by the environment, requiring consideration of external force field variations for accurate structure prediction. The fuzzy oil drop model reveals the importance of environmental factors in determining protein structures, highlighting the need for a more comprehensive approach in protein structure prediction.
BMC BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)