Randall Division of Cell and Molecular Biophysics

About: Randall Division of Cell and Molecular Biophysics is a based out in . It is known for research contribution in the topics: Actin cytoskeleton & Skeletal muscle. The organization has 576 authors who have published 1229 publications receiving 78279 citations.

Specialized Dynamical Properties of Promiscuous Residues Revealed by Simulated Conformational Ensembles

Abstract: The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calcul...

Control of erythrocyte membrane-skeletal cohesion by the spectrin-membrane linkage.

Abstract: Spectrin tetramer is the major structural member of the membrane-associated skeletal network of red cells. We show here that disruption of the spectrin-ankyrin-band 3 link to the membrane leads to dissociation of a large proportion of the tetramers into dimers. Noncovalent perturbation of the linkage was induced by a peptide containing the ankyrin-binding site of the spectrin beta-chain, and covalent perturbation by treatment with the thiol reagent, N-ethylmaleimide (NEM). This reagent left the intrinsic self-association capacity of the spectrin dimers unaffected and disturbed only the ankyrin-band 3 interaction. The dissociation of spectrin tetramers on the membrane into functional dimers was confirmed by the binding of a spectrin peptide directed against the self-association sites. Dissociation of the tetramers resulted, we infer, from detachment of the proximal ends of the constituent dimers from the membrane, thereby reducing their proximity to one another and thus weakening their association. The measured affinity of the interaction of the peptides with the free dimer ends on the membrane permits an estimate of the equilibrium between intact and dissociated tetramers on the native membrane. This indicates that in the physiological state the equilibrium proportion of the dissociated tetramers may be as high as 5-10%. These findings enabled us to identify an additional important functional role for the spectrin-ankyrin-band 3 link in regulating spectrin self-association in the red cell membrane.

Integrating Receptor Signal Inputs That Influence Small Rho GTPase Activation Dynamics at the Immunological Synapse

Abstract: The Rho GTPase Cdc42 regulates cytoskeletal changes at the immunological synapse (IS) that are critical to T-cell activation. By imaging fluorescent activity biosensors (Raichu) using fluorescence lifetime imaging microscopy, Cdc42 activation was shown to display kinetics that are conditional on the specific receptor input (through two IS-associated receptors, CD3 and β1 integrin). CD3-triggered Cdc42 activity is dependent on the cyto-2 (NPIY) motif of the β1 integrin cytoplasmic domain. Perturbations of the ezrin-radixin-moesin (ERM) function blocked CD3- and β1-dependent increases in Cdc42 activity. Both IS-associated receptors probably lie on a serial molecular pathway and transduce signals through the ERM-dependent machinery that is responsible for the remodeling and stabilization of the synapse. Cdc42 activity is impaired in β1 integrin-deficient T cells that form conjugates with antigen-presenting cells but is partially restored in the context of an antigen-specific synapse. This restoration of Cdc42 activity is due, at least in part, to the recruitment and activation of β2 integrin.