38 research outputs found
Beyond icosahedral symmetry in packings of proteins in spherical shells
The formation of quasi-spherical cages from protein building blocks is a
remarkable self-assembly process in many natural systems, where a small number
of elementary building blocks are assembled to build a highly symmetric
icosahedral cage. In turn, this has inspired synthetic biologists to design de
novo protein cages. We use simple models, on multiple scales, to investigate
the self-assembly of a spherical cage, focusing on the regularity of the
packing of protein-like objects on the surface. Using building blocks, which
are able to pack with icosahedral symmetry, we examine how stable these highly
symmetric structures are to perturbations that may arise from the interplay
between flexibility of the interacting blocks and entropic effects. We find
that, in the presence of those perturbations, icosahedral packing is not the
most stable arrangement for a wide range of parameters; rather disordered
structures are found to be the most stable. Our results suggest that (i) many
designed, or even natural, protein cages may not be regular in the presence of
those perturbations, and (ii) that optimizing those flexibilities can be a
possible design strategy to obtain regular synthetic cages with full control
over their surface properties.Comment: 8 pages, 5 figure
Expression and retention of thymidine phosphorylase in cultured reticulocytes as a novel treatment for MNGIE
Identification of the Initial Steps in Signal Transduction in the α4β2 Nicotinic Receptor:Insights from Equilibrium and Nonequilibrium Simulations
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors and suggest subtype specificity
A conserved arginine with non-conserved function is a key determinant of agonist selectivity in α7 nicotinic ACh receptors
The α7 and α4β2* (“*” denotes possibly assembly with another subunit) nicotinic acetylcholine receptors (nAChRs) are the most abundant nAChRs in the mammalian brain. These receptors are the most targeted nAChRs in drug discovery programmes for brain disorders. However, the development of subtype-specific agonists remains challenging due to the high degree of sequence homology and conservation of function in nAChRs. We have developed C(10) variants of cytisine, a partial agonist of α4β2 nAChR that has been used for smoking cessation. The C(10) methyl analogue used in this study displays negligible affinity for α7 nAChR, while retaining high affinity for α4β2 nAChR.Fil: Minguez Viñas, Teresa. Oxford Brookes University; Reino UnidoFil: Nielsen, Beatriz Elizabeth. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; ArgentinaFil: Shoemark, Deborah K.. University Of Bristol; Reino UnidoFil: Gotti, Cecilia. UniversitĂ degli Studi di Milano; ItaliaFil: Sessions, Richard B.. University Of Bristol; Reino UnidoFil: Mulholland, Adrian J.. University Of Bristol; Reino UnidoFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; ArgentinaFil: Wonnacott, Susan. University of Bath; Reino UnidoFil: Gallagher, Timothy. University Of Bristol; Reino UnidoFil: Bermudez, Isabel. University of Oxford; Reino UnidoFil: Oliveira, Ana Sofia. University Of Bristol; Reino Unid