Article
Biochemistry & Molecular Biology
Irene Noro, Ilaria Bettin, Sabrina Fasoli, Marcello Smania, Luca Lunardi, Michele Giannini, Leonardo Andreoni, Riccardo Montioli, Giovanni Gotte
Summary: Human RNase 1 and bovine RNase A are prototypes of the pt-RNase superfamily and can oligomerize through the 3D domain swapping mechanism. RNase 1 self-associates through the 3D-DS of its N- and C-termini, while RNase A only forms N-swapped dimers. RNase 1 exhibits a higher tendency to self-associate than RNase A, and its C-terminus plays a specific role in the oligomerization of different RNases.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Giovanni Gotte, Elena Butturini, Ilaria Bettin, Irene Noro, Alexander Mahmoud Helmy, Andrea Fagagnini, Barbara Cisterna, Manuela Malatesta
Summary: RNase A can form oligomers through the 3D domain swapping mechanism. These oligomers can evolve into large aggregates called super-aggregates (SAs), which are not derived from native RNase A monomers or oligomers with C-terminus swapping. Two subunits' N-termini swapping is required for SA formation. SAs retain low ribonucleolytic activity and are confirmed to be derived from RNase A. TEM analyses and Thioflavin-T (ThT) interactions indicate that SAs are large and circular, but not amyloid-like derivatives. These findings suggest that the opening of RNase A N-terminus and 3D-DS-mediated oligomerization may be a preliminary step in massive RNase A aggregation. The study provides insights into protein aggregation and its potential applications in combating amyloidosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zhiliang Yuan, Zhi Qu, Bo Duan, Tianyi Wang, Jiajun Xu, Bin Xia
Summary: The C-terminal domain of M-pro-C can form a 3D domain-swapped dimer and amyloid fibrils under non-denaturing and 3D domain-swappable conditions, respectively. Positive correlations between domain swapping dimerization rates and amyloid fibrillation were found, but not essential, as mutants incapable of 3D domain swapping could still form fibrils. The unpacking of the protofibril core region during 3D domain swapping accelerates the amyloid fibrillation process.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Do-Hee Kim, Youngseo Na, Heesun Chang, Jun-Hyuk Boo, Sung-Min Kang, Chenglong Jin, Su-Jin Kang, Su Yeon Lee, Bong-Jin Lee
Summary: Polyketide metabolism-associated proteins in Mycobacterium tuberculosis are crucial for the survival of the bacterium, making them potential drug targets for tuberculosis treatment. This study focuses on the structural and functional characterization of a novel ribonuclease protein, Rv1546, which belongs to the steroidogenic acute regulatory protein-related lipid-transfer (START) domain superfamily. The crystal structure of Rv1546 in a V-shaped dimer is determined, and it forms a helix-grip fold through three-dimensional domain swapping. Site-directed mutagenesis and ribonuclease activity assays identify important catalytic sites of Rv1546. Overall, these findings provide new insights into the potential of Rv1546 as a drug target for tuberculosis treatment.
Article
Chemistry, Physical
Maria Celeste Maschio, Jacopo Fregoni, Carla Molteni, Stefano Corni
Summary: The protein beta(2)-microglobulin can aggregate in insoluble amyloid fibrils, which deposit in the skeletal muscle system of patients undergoing long-term haemodialysis. Research has shown that the isomerization of a specific proline (Pro32) in beta(2)-m plays a key role in stabilizing and destabilizing the two isomers.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Kritika Kumari, Marina Warepam, Aniket Kumar Bansal, Tanveer Ali Dar, Vladimir N. Uversky, Laishram Rajendrakumar Singh
Summary: TMAO is a significant metabolite derived from various organic compounds, with diverse biological functions in humans. Studies have shown its crucial impact on protein folding and cell cycle, potentially leading to protein misfolding and the development of related diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
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
Sabrina Fasoli, Ilaria Bettin, Riccardo Montioli, Andrea Fagagnini, Daniele Peterle, Douglas V. Laurents, Giovanni Gotte
Summary: Human Angiogenin (hANG) is a protein that promotes vessel formation and is associated with diseases like PD and ALS. Research shows that ANG can form enzymatically active dimers through three-dimensional domain swapping, which could be crucial in understanding its role in neurodegenerative pathologies in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Zihan Zhao, Xuejiao Xu, Hairong Cheng, Michelle C. Miller, Zhen He, Hongming Gu, Zhongyu Zhang, Avraham Raz, Kevin H. Mayo, Guihua Tai, Yifa Zhou
Summary: Gal-3's N-terminal tail with proline-rich residues plays a crucial role in mediating various cellular activities, affecting cell migration, activation, endocytosis, and hemagglutination. The research also reveals the significant impact of prolines in regulating Gal-3 oligomerization process.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Connie A. Tenorio, Joseph B. Parker, Michael Blaber
Summary: Successful protein design requires considering folding kinetics, stability thermodynamics, and biochemical functionality. The design can be simplified by separating it into two steps: initial design of a protein scaffold and subsequent functional mutation. This approach allows for broader functional adaptation.
Article
Biochemistry & Molecular Biology
Marton Fogarasi, Simona Dima
Summary: Homomultimerization of MT1-MMP through different domains is crucial for its proteolytic activity and the binding affinity to type I collagen. The catalytic domain of MT1-MMP is necessary and sufficient to mediate the formation of multimeric structures.
Article
Biochemistry & Molecular Biology
Lorenzo Visconti, Francesca Malagrino, Francesca Troilo, Livia Pagano, Angelo Toto, Stefano Gianni
Summary: This study elucidates the folding and unfolding mechanisms of the multi-domain protein Whirlin, focusing on the PDZ1 and PDZ2 domains. The difference in thermodynamic stability of these domains leads to the accumulation of a misfolded intermediate. The experimental and analytical approaches presented in this study offer valuable insights for understanding complex multi-domain protein folding kinetics.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Charlotte Rat, Cedric Heindl, Hannes Neuweiler
Summary: Domain swap is a mechanism of protein dimerization in which two interacting domains exchange parts of their structure. Spidroin CTDs play a critical role in silk formation by inducing structural transitions, and the domain swap of spidroin CTDs results in an entropic penalty that prepares them for refolding during silk formation.
Review
Chemistry, Physical
Mahesh Narayan
Summary: This review article discusses the role of non-native disulfide bond-containing species in oxidative protein folding, and explores their existence by projecting the regeneration pathway onto a Cartesian coordinate system and superimposing the folding funnel onto the regeneration trajectory.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemistry & Molecular Biology
Nuno F. B. Oliveira, Filipe E. P. Rodrigues, Joao N. M. Vitorino, Rui J. S. Loureiro, Patricia F. N. Faisca, Miguel Machuqueiro
Summary: The study used the D76N mutant as a model to investigate protein aggregation, finding that hydrophobic interactions play a major role in stabilizing interfaces in a series of dimers at physiological pH. The most stable binding mode exhibits self-limited growth properties, while less stable interfaces can propagate indefinitely to form long polymerized chains.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
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)