About: Conformational change is a(n) research topic. Over the lifetime, 6060 publication(s) have been published within this topic receiving 226811 citation(s).
Papers published on a yearly basis
TL;DR: This purified system of five purified proteins should facilitate understanding of how eukaryotlc hsp70 and hsp90 work together as essential components of a process that alters the conformations of substrate proteins to states that respond in signal transduction.
Abstract: Nearly 100 proteins are known to be regulated by hsp90. Most of these substrates or "client proteins" are involved in signal transduction, and they are brought into complex with hsp90 by a multiprotein hsp90/hsp70-based chaperone machinery. In addition to binding substrate proteins at the chaperone site(s), hsp90 binds cofactors at other sites that are part of the heterocomplex assembly machinery as well as immunophilins that connect assembled substrate*hsp90 complexes to protein-trafficking systems. In the 5 years since we last reviewed this subject, much has been learned about hsp90 structure, nucleotide-binding, and cochaperone interactions; the most important concept is that ATP hydrolysis by an intrinsic ATPase activity results in a conformational change in hsp90 that is required to induce conformational change in a substrate protein. The conformational change induced in steroid receptors is an opening of the steroid-binding cleft so that it can be accessed by steroid. We have now developed a minimal system of five purified proteins-hsp90, hsp70, Hop, hsp40, and p23- that assembles stable receptor*hsp90 heterocomplexes. An hsp90*Hop*hsp70*hsp40 complex opens the cleft in an ATP-dependent process to produce a receptor*hsp90 heterocomplex with hsp90 in its ATP-bound conformation, and p23 then interacts with the hsp90 to stabilize the complex. Stepwise assembly experiments have shown that hsp70 and hsp40 first interact with the receptor in an ATP-dependent reaction to produce a receptor*hsp70*hsp40 complex that is "primed" to be activated to the steroid-binding state in a second ATP-dependent step with hsp90, Hop, and p23. Successful use of the five-protein system with other substrates indicates that it can assemble signal protein*hsp90 heterocomplexes whether the substrate is a receptor, a protein kinase, or a transcription factor. This purified system should facilitate understanding of how eukaryotic hsp70 and hsp90 work together as essential components of a process that alters the conformations of substrate proteins to states that respond in signal transduction.
TL;DR: It is shown that a highly bent integrin conformation is physiological and has low affinity for biological ligands.
Abstract: How ligand binding alters integrin conformation in outside-in signaling, and how inside-out signals alter integrin affinity for ligand, have been mysterious. We address this with electron microscopy, physicochemical measurements, mutational introduction of disulfides, and ligand binding to alphaVbeta3 and alphaIIbbeta3 integrins. We show that a highly bent integrin conformation is physiological and has low affinity for biological ligands. Addition of a high affinity ligand mimetic peptide or Mn(2+) results in a switchblade-like opening to an extended structure. An outward swing of the hybrid domain at its junction with the I-like domain shows conformational change within the headpiece that is linked to ligand binding. Breakage of a C-terminal clasp between the alpha and beta subunits enhances Mn(2+)-induced unbending and ligand binding.
TL;DR: The crystallographic structure of a typical serpin–protease complex is reported and the mechanism of inhibition is shown, showing the ability of the conformational mechanism to crush as well as inhibit proteases that provides the serpins with their selective advantage.
Abstract: The serpins have evolved to be the predominant family of serine-protease inhibitors in man. Their unique mechanism of inhibition involves a profound change in conformation, although the nature and significance of this change has been controversial. Here we report the crystallographic structure of a typical serpin-protease complex and show the mechanism of inhibition. The conformational change is initiated by reaction of the active serine of the protease with the reactive centre of the serpin. This cleaves the reactive centre, which then moves 71 A to the opposite pole of the serpin, taking the tethered protease with it. The tight linkage of the two molecules and resulting overlap of their structures does not affect the hyperstable serpin, but causes a surprising 37% loss of structure in the protease. This is induced by the plucking of the serine from its active site, together with breakage of interactions formed during zymogen activation. The disruption of the catalytic site prevents the release of the protease from the complex, and the structural disorder allows its proteolytic destruction. It is this ability of the conformational mechanism to crush as well as inhibit proteases that provides the serpins with their selective advantage.
TL;DR: The experiments show that an isomerization of DNA with a certain base sequence is possible in solution and the proposed model suggests a plausible mechanism.
Abstract: A reversible intramolecular and co-operative isomerization of double-stranded, oligomeric and poly(dG-dC) · poly(dG-dC) takes place in aqueous solution when the salt concentration at 25 °C and neutral pH is increased to 2.5 m-NaCl, 1.8 m-NaClO4 or 0.7 m-MgCl2. This conformational transition between two different double helical forms is accompanied by changes of optical rotatory dispersion, circular dichroism and ultraviolet absorption. Preliminary X-ray diffraction data are compatible with the existence of two salt-dependent structures. The enthalpy change of the transition is close to zero. The first-order kinetics are in the time range of 102 to 103 seconds and are followed after appropriate shifts in the salt concentration. The activation energy for both over-all rate constants is + 22 ± 2 kcal./mole and is nearly independent of the chain length. In chloride solutions the over-all rate constant for the transition from the high salt L-form to the low salt R-form decreases strongly with increasing salt concentrations. A detailed mechanism is proposed involving for the nucleation of the other helical form the opening or unstacking of a certain number of base pairs at the end of an oligomer. Analytical expressions for the chain length dependence of the degree of transition and the relaxation time are derived, assuming steady-state conditions for intermediates. The experiments show that an isomerization of DNA with a certain base sequence is possible in solution and the proposed model suggests a plausible mechanism. Some biological implications of such conformational transitions in DNA are briefly discussed.
TL;DR: This work proposes a fusion mechanism driven by essentially irreversible conformational changes in E and facilitated by fusion-loop insertion into the outer bilayer leaflet, and suggests strategies for inhibiting flavivirus entry.
Abstract: Dengue virus enters a host cell when the viral envelope glycoprotein, E, binds to a receptor and responds by conformational rearrangement to the reduced pH of an endosome. The conformational change induces fusion of viral and host-cell membranes. A three-dimensional structure of the soluble E ectodomain (sE) in its trimeric, postfusion state reveals striking differences from the dimeric, prefusion form. The elongated trimer bears three ‘fusion loops’ at one end, to insert into the host-cell membrane. Their structure allows us to model directly how these fusion loops interact with a lipid bilayer. The protein folds back on itself, directing its carboxy terminus towards the fusion loops. We propose a fusion mechanism driven by essentially irreversible conformational changes in E and facilitated by fusion-loop insertion into the outer bilayer leaflet. Specific features of the folded-back structure suggest strategies for inhibiting flavivirus entry.