More Like this

1. Disordered proteins interact with the chemical environment to tune their protective function during drying

   https://doi.org/10.7554/elife.97231.3  

   KC, Shraddha; Nguyen, Kenny H; Nicholson, Vincent; Walgren, Annie; Trent, Tony; Gollub, Edith; Romero-Perez, Paulette Sofia; Holehouse, Alex S; Sukenik, Shahar; Boothby, Thomas C (November 2024, eLife)

   The conformational ensemble and function of intrinsically disordered proteins (IDPs) are sensitive to their solution environment. The inherent malleability of disordered proteins, combined with the exposure of their residues, accounts for this sensitivity. One context in which IDPs play important roles that are concomitant with massive changes to the intracellular environment is during desiccation (extreme drying). The ability of organisms to survive desiccation has long been linked to the accumulation of high levels of cosolutes such as trehalose or sucrose as well as the enrichment of IDPs, such as late embryogenesis abundant (LEA) proteins or cytoplasmic abundant heat-soluble (CAHS) proteins. Despite knowing that IDPs play important roles and are co-enriched alongside endogenous, species-specific cosolutes during desiccation, little is known mechanistically about how IDP-cosolute interactions influence desiccation tolerance. Here, we test the notion that the protective function of desiccation-related IDPs is enhanced through conformational changes induced by endogenous cosolutes. We find that desiccation-related IDPs derived from four different organisms spanning two LEA protein families and the CAHS protein family synergize best with endogenous cosolutes during drying to promote desiccation protection. Yet the structural parameters of protective IDPs do not correlate with synergy for either CAHS or LEA proteins. We further demonstrate that for CAHS, but not LEA proteins, synergy is related to self-assembly and the formation of a gel. Our results suggest that functional synergy between IDPs and endogenous cosolutes is a convergent desiccation protection strategy seen among different IDP families and organisms, yet the mechanisms underlying this synergy differ between IDP families. 

   more » « less
2. Disordered proteins interact with the chemical environment to tune their protective function during drying

   https://doi.org/10.7554/elife.97231.1  

   KC, Shraddha; Nguyen, Kenny; Nicholson, Vincent; Walgren, Annie; Trent, Tony; Gollub, Edith; Romero, Sofia; Holehouse, Alex S; Sukenik, Shahar; Boothby, Thomas C (June 2024, eLife)

   The conformational ensemble and function of intrinsically disordered proteins (IDPs) are sensitive to their solution environment. The inherent malleability of disordered proteins combined with the exposure of their residues accounts for this sensitivity. One context in which IDPs play important roles that is concomitant with massive changes to the intracellular environment is during desiccation (extreme drying). The ability of organisms to survive desiccation has long been linked to the accumulation of high levels of cosolutes such as trehalose or sucrose as well as the enrichment of IDPs, such as late embryogenesis abundant (LEA) proteins or cytoplasmic abundant heat soluble (CAHS) proteins. Despite knowing that IDPs play important roles and are co-enriched alongside endogenous, species-specific cosolutes during desiccation, little is known mechanistically about how IDP-cosolute interactions influence desiccation tolerance. Here, we test the notion that the protective function of desiccation-related IDPs is enhanced through conformational changes induced by endogenous cosolutes. We find that desiccation-related IDPs derived from four different organisms spanning two LEA protein families and the CAHS protein family, synergize best with endogenous cosolutes during drying to promote desiccation protection. Yet the structural parameters of protective IDPs do not correlate with synergy for either CAHS or LEA proteins. We further demonstrate that for CAHS, but not LEA proteins, synergy is related to self-assembly and the formation of a gel. Our results demonstrate that functional synergy between IDPs and endogenous cosolutes is a convergent desiccation protection strategy seen among different IDP families and organisms, yet, the mechanisms underlying this synergy differ between IDP families. 

   more » « less
3. Linear and Nonlinear Dielectric Response of Intrinsically Disordered Proteins

   https://doi.org/10.1021/acs.jpclett.4c00866  

   Sauer, Michael A; Colburn, Taylor; Maiti, Sthitadhi; Heyden, Matthias; Matyushov, Dmitry V (May 2024, The Journal of Physical Chemistry Letters)

   Scholes, Gregory D (Ed.)

   Linear and nonlinear dielectric responses of solutions of intrinsically disordered proteins (IDPs) were analyzed by combining molecular dynamics simulations with formal theories. A large increment of the linear dielectric function over that of the solvent is found and related to large dipole moments of IDPs. The nonlinear dielectric effect (NDE) of the IDP far exceeds that of the bulk electrolyte, offering a route to interrogate protein conformational and rotational statistics and dynamics. Conformational flexibility of the IDP makes the dipole moment statistics consistent with the gamma/log-normal distributions and contributes to the NDE through the dipole moment’s non-Gaussian parameter. The intrinsic non-Gaussian parameter of the dipole moment combines with the protein osmotic compressibility in the nonlinear dielectric susceptibility when dipolar correlations are screened by the electrolyte. The NDE is dominated by dipolar correlations when electrolyte screening is reduced. 

   more » « less
4. The origin and impact of bound water around intrinsically disordered proteins

   https://doi.org/https://doi.org/10.1016/j.bpj.2022.01.011  

   Reid, Korey M.; Singh, Abhishek K.; Bikash, Chowdhury R.; Wei, Jessica; Tal-Gan, Yftah; Vinh, Nguyen Q.; Leitner, David M. (January 2022, Biophysical journal)

   Proteins and water couple dynamically over a wide range of time scales. Motivated by their central role in protein function, protein-water dynamics and thermodynamics have been extensively studied for structured proteins, where correspondence to structural features has been made. However, properties controlling intrinsically disordered protein (IDP)-water dynamics are not yet known. We report results of megahertz-to-terahertz dielectric spectroscopy and molecular dynamics simulations of a group of IDPs with varying charge content along with structured proteins of similar size. Hydration water around IDPs is found to exhibit more heterogeneous rotational and translational dynamics compared with water around structured proteins of similar size, yielding on average more restricted dynamics around individual residues of IDPs, charged or neutral, compared with structured proteins. The on-average slower water dynamics is found to arise from excess tightly bound water in the first hydration layer, which is related to greater exposure to charged groups. The more tightly bound water to IDPs correlates with the smaller hydration shell found experimentally, and affects entropy associated with protein-water interactions, the contribution of which we estimate based on the dielectric measurements and simulations. Water-IDP dynamic coupling at terahertz frequencies is characterized by the dielectric measurements and simulations. 

   more » « less
5. Mass proxy quality of massive halo properties in the illustrisTNG and flamingo simulations: I. Hot gas

   https://doi.org/10.1093/mnras/staf1665  

   Aljamal, Eddie; Evrard, August E; Farahi, Arya; Pillepich, Annalisa; Nelson, Dylan; Schaye, Joop; Schaller, Matthieu; Braspenning, Joey (October 2025, Monthly Notices of the Royal Astronomical Society)

   ABSTRACT We examine scale and redshift dependence of mass–property relations (MPRs) for five hot gas properties of two large group- bservationsand cluster-scale halo samples realized by the Illustris tng, TNG-Cluster, and FLAMINGO cosmological hydrodynamical simulations. For intrinsic properties of (i) hot gas mass ($$M_{\rm gas}$$), (ii) spectroscopic-like temperature ($$T_{\rm sl}$$), (iii) soft-band X-ray luminosity ($$L_{\rm X}$$), and (iv) X-ray ($$Y_{\rm X}$$), and (v) Sunyaev–Zel’dovich ($$Y_{\rm SZ}$$) thermal energies, we use MPR parameters to infer mass proxy quality (MPQ) – the implied scatter in total halo mass conditioned on a property – for haloes with $$M_{\rm 500c}\ge 10^{13}\, {\rm M}_\odot$$ at redshifts, $$z \in \lbrace 0, 0.5, 1, 2\rbrace$$. We find: (1) in general, scaling relation slopes and covariance display moderate to strong dependence on halo mass, with redshift dependence secondary; (2) for haloes with $$M_{\rm 500c}> 10^{14}\, {\rm M}_\odot$$, scalings of $$M_{\rm gas}$$ and $$Y_{\rm SZ}$$ simplify toward self-similar slope and constant intrinsic scatter (5 and 10 per cent, respectively) nearly independent of scale, making both measures ideal for cluster finding and characterization to $z=2$; (3) halo mass-conditioned likelihoods of hot gas mass and thermal energy closely follow a lognormal form; and (4) despite normalization differences up to 0.4 dex between the two simulations, higher order scaling features such as slopes and property covariance show much better agreement. Slopes show appreciable redshift dependence at the group scale, while redshift dependence of the scatter is exhibited by low-mass flamingo haloes only; (5) property correlations are largely consistent between the simulations, with values that mainly agree with existing empirical measurements. We close with a literature survey placing our MPR slopes and intrinsic scatter estimates into community context. 

   more » « less