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Symmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin.
Proc Natl Acad Sci U S A
January 2025
Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637.
Many proteins form paralogous multimers-molecular complexes in which evolutionarily related proteins are arranged into specific quaternary structures. Little is known about the mechanisms by which they acquired their stoichiometry (the number of total subunits in the complex) and heterospecificity (the preference of subunits for their paralogs rather than other copies of the same protein). Here, we use ancestral protein reconstruction and biochemical experiments to study historical increases in stoichiometry and specificity during the evolution of vertebrate hemoglobin (Hb), an αβ heterotetramer that evolved from a homodimeric ancestor after a gene duplication.
View Article and Find Full Text PDFModeling Innate Immunity Causing Chronic Inflammation and Tissue Damage.
Bull Math Biol
January 2025
Department of Biology, Faculty of Science, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, 819-0395, Japan.
Mathematical models of immune responses have traditionally focused on adaptive immunity and pathogen-immune dynamics. However, recent advances in immunology have highlighted the critical role of innate immunity. In response to physical damage or pathogen attacks, innate immune cells circulating throughout the body rapidly migrate from blood vessels and accumulate at the site of injury, triggering inflammation.
View Article and Find Full Text PDFKey Structural Features of Microvascular Networks Leading to the Formation of Multiple Equilibria.
Bull Math Biol
January 2025
Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Woodstock Rd, Oxford, Oxfordshire, OX2 6GG, UK.
We analyse mathematical models of blood flow in two simple vascular networks in order to identify structural features that lead to the formation of multiple equilibria. Our models are based on existing rules for blood rheology and haematocrit splitting. By performing bifurcation analysis on these simple network flow models, we identify a link between the changing flow direction in key vessels and the existence of multiple equilibria.
View Article and Find Full Text PDFPhenomenological Modeling of Antibody Response from Vaccine Strain Composition.
Antibodies (Basel)
January 2025
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
The elicitation of broadly neutralizing antibodies (bnAbs) is a major goal of vaccine design for highly mutable pathogens, such as influenza, HIV, and coronavirus. Although many rational vaccine design strategies for eliciting bnAbs have been devised, their efficacies need to be evaluated in preclinical animal models and in clinical trials. To improve outcomes for such vaccines, it would be useful to develop methods that can predict vaccine efficacies against arbitrary pathogen variants.
View Article and Find Full Text PDFPeptide Inhibitor Assay for Allocating Functionally Important Accessible Sites Throughout a Protein Chain: Restriction Endonuclease EcoRI as a Model Protein System.
BioTech (Basel)
December 2024
The BCPH Unit of Molecular Physiology, Department of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Nishihara 903-0213, Okinawa, Japan.
Functionally important amino acid sequences in proteins are often located at multiple sites. Three-dimensional structural analysis and site-directed mutagenesis may be performed to allocate functional sites for understanding structure‒function relationships and for developing novel inhibitory drugs. However, such methods are too demanding to comprehensively cover potential functional sites throughout a protein chain.
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