Capturing nested information from disordered peptide phases

Abstract

Anfinsen's dogma emerged from experiments which show that a protein's native 3D folded architecture is encoded within its primary sequence. This insight emerged before almost 40% of eukaryotic proteins were found to contain intrinsically disordered domains with binding partners that are able to template multiple structures and functional outputs. Despite the challenges associated with characterizing such intrinsically disordered protein domains and their interactions with various binding partners, the need to understand how they propagate and regulate context-dependent information now becomes increasingly important. In addition to understanding the complex signaling networks of multicellular organisms, harness their potential will expand the next generation of functional materials. Accordingly, we review progress with model peptides to reveal the rules necessary for precise spatiotemporal assembly of polypeptide materials.

Systems chemistry of peptide-assemblies for biochemical transformations

“…69,150,191 It is important to note that detailed studies on molecular interactions among the amino acid residues to achieve particular secondary and higher order structures have been well established by the research laboratories of Ulijn, Gazit, Lynn and others. 55,56,189,[192][193][194][195][196][197] Despite the limits of the short peptide sequence, via judicious installation of specific active site functional groups and hydrophobic residues, diverse catalytic functions can be targeted by these peptide microphases (Fig. 12).…”

“…69,150,191 It is important to note that detailed studies on molecular interactions among the amino acid residues to achieve particular secondary and higher order structures have been well established by the research laboratories of Ulijn, Gazit, Lynn and others. 55,56,189,192–197…”

Polyanion order controls liquid-to-solid phase transition in peptide/nucleic acid co-assembly

“…The functions of these cellular membraneless organelles range from storage granules to processing hubs chaperoning mRNA through the critical stages of cellular stress, division, and differentiation ( Alberti et al, 2017 ; Shin and Brangwynne, 2017 ; Alberti et al, 2019 ; Tauber et al, 2020 ). The multifaceted functions that RNP granules play depends on dynamic structural plasticity of these co-assemblies ( Banani et al, 2017 ; Boeynaems et al, 2019 ; Conicella et al, 2020 ; Dutagaci et al, 2021 ; Gordon et al, 2021 ; Hallegger et al, 2021 ; Carey and Guo, 2022 ). For example, the cooperative interactions between arginine residues of the RNA binding domain and the tyrosine residues from the prion-like domains (PLD) of FUS are critical for the dual effects of ATP concentrations that both induces and inhibits initial phase transitions at different concentrations by controlling these interactions ( Wang et al, 2018 ; Ren et al, 2022 ).…”

“…The nucleating core of the Alzheimer’s disease-associated Aβ42 peptide, the sequence KLVFFAE, has been extensively studied as a separate peptide and shown to have strong cross- β propensity: independently undergoing two-step nucleation that includes condensation and subsequent self-assembly into cross- β fibers, which can allow for the inclusion of other polymers between the leaflets ( Figure 1 ). There is now evidence that these peptide condensates are preordered within the condensates for nucleation, highlighting the remarkable potential environmental control over the final assembled morphology ( Mehta et al, 2008 ; Childers et al, 2012 ; Mehta et al, 2013 ; Uversky, 2013 ; Liang et al, 2014 ; Arai et al, 2015 ; Mollica et al, 2016 ; Hsieh et al, 2017a ; Kim and Han, 2018 ; Gordon et al, 2021 ; Hallegger et al, 2021 ). Indeed, subtle changes in amino acid sequence greatly impact the rates of nucleation and propagation along the three potential cross- β assembly growth planes.…”