Slow dynamics measured by phosphorescence lifetime reveals global conformational changes in human adult hemoglobin induced by allosteric effectors.

The mechanism underlying allostery in hemoglobin (Hb) is still not completely understood. Various models describing the action of allosteric effectors on Hb function have been published in the literature. It has also been reported that some allosteric effectors-such as chloride ions, inositol hexaphosphate, 2,3-diphospho-glycerate and bezafibrate-considerably lower the oxygen affinity of Hb.

Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways upon exposure to cough-generated droplets and aerosol particles.

The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Pseudouridylation defect due to and mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis.

RNA modifications play a fundamental role in cellular function. Pseudouridylation, the most abundant RNA modification, is catalyzed by the H/ACA small ribonucleoprotein (snoRNP) complex that shares four core proteins, dyskerin (DKC1), NOP10, NHP2, and GAR1. Mutations in , , or cause dyskeratosis congenita (DC), a disorder characterized by telomere attrition.

C-terminal oligomerization of podocin mediates interallelic interactions.

Interallelic interactions of membrane proteins are not taken into account while evaluating the pathogenicity of sequence variants in autosomal recessive disorders. Podocin, a membrane-anchored component of the slit diaphragm, is encoded by NPHS2, the major gene mutated in hereditary podocytopathies. We formerly showed that its R229Q variant is only pathogenic when trans-associated to specific 3' mutations and suggested the causal role of an abnormal C-terminal dimerization.

Dissimilar flexibility of α and β subunits of human adult hemoglobin influences the protein dynamics and its alteration induced by allosteric effectors.

The general question by what mechanism an "effector" molecule and the hemes of hemoglobin interact over widely separated intramolecular distances to change the oxygen affinity has been extensively investigated, and still has remained of central interest. In the present work we were interested in clarifying the general role of the protein matrix and its dynamics in the regulation of human adult hemoglobin (HbA). We used a spectroscopy approach that yields the compressibility (κ) of the protein matrix around the hemes of the subunits in HbA and studied how the binding of heterotropic allosteric effectors modify this parameter.

Without Binding ATP, Human Rad51 Does Not Form Helical Filaments on ssDNA.

Construction of the presynaptic filament (PSF) of proper helical structure by Rad51 recombinases is a prerequisite of the progress of homologous recombination repair. We studied the contribution of ATP-binding to this structure of wt human Rad51 (hRad51). We exploited the protein-dissociation effect of high hydrostatic pressure to determine the free energy of dissociation of the protomer interfaces in hRad51 oligomer states and used electron microscopy to obtain topological parameters.

Role of domain interactions in the collective motion of phosphoglycerate kinase.

Protein function is governed by the underlying conformational dynamics of the molecule. The experimental and theoretical work leading to contemporary understanding of enzyme dynamics was mostly restricted to the large-scale movements of single-domain proteins. Collective movements resulting from a regulatory interplay between protein domains is often crucial for enzymatic activity.

Conformational dynamics of titin PEVK explored with FRET spectroscopy.

The proline-, glutamate-, valine-, and lysine-rich (PEVK) domain of the giant muscle protein titin is thought to be an intrinsically unstructured random-coil segment. Various observations suggest, however, that the domain may not be completely devoid of internal interactions and structural features. To test the validity of random polymer models for PEVK, we determined the mean end-to-end distances of an 11- and a 21-residue synthetic PEVK peptide, calculated from the efficiency of the fluorescence resonance energy transfer (FRET) between an N-terminal intrinsic tryptophan donor and a synthetically added C-terminal IAEDANS acceptor obtained in steady-state and time-resolved experiments.

Millisecond time-scale protein dynamics exists prior to the activation of the bulk solvent matrix.

Conformational dynamics of proteins is of fundamental importance in their physiological functions. The exact mechanisms and determinants of protein motions, including the regulatory interplay between protein and solvent motions, are not yet fully understood. In the present work, the thermal activation of phosphorescence quenching was measured in oxygen-saturated aqueous protein solutions to explore protein dynamics in the millisecond range.

Allosteric effectors influence the tetramer stability of both R- and T-states of hemoglobin A.

The contribution of heterotropic effectors to hemoglobin allostery is still not completely understood. With the recently proposed global allostery model, this question acquires crucial significance, because it relates tertiary conformational changes to effector binding in both the R- and T-states. In this context, an important question is how far the induced conformational changes propagate from the binding site(s) of the allosteric effectors.