Biology subjects

Bohl, J.

Publications and source records attributed to Bohl, J..

2 recordsLinked to original sources

bioRxiv2026

Non-fibrillar prion protein oligomers transmit structural information during early assembly

The prion paradigm is founded on the transmission of structural information from aggregated assemblies to soluble protein substrates, a process classically attributed to fibril-end-mediated templating. Whether non-fibrillar assemblies or transient oligomeric states can also participate in folding information transfer remains unclear. Here, using recombinant prion protein (PrP), rational mutagenesis, hetero-oligomerization assays, arrested reaction conditions, and single-particle atomic force microscopy coupled to infrared nano-spectroscopy (AFM-IR), we examine the earliest stages of PrP assembly from the perspective of folding information transmission. We show that polymerization-defective PrP variants can be incorporated into oligomeric assemblies through structural complementation, in which folding information supplied by wild-type PrP restores their assembly competence. Under arrested reaction conditions, transient polymerization-competent conformers further contribute to folding information transfer at subcritical concentrations. Domain-resolved analyses reveal a modular oligomeric architecture in which a {beta}-sheet-rich B domain constitutes the primary scaffold for folding information transfer. Preformed O1 oligomers then act as autonomous conformational templates that promote mutant incorporation and undergo hierarchical condensation through accretion of a structurally distinct E domain. Together, these findings demonstrate that non-fibrillar PrP oligomers and transient assembly intermediates can store and transmit folding information and may function as oligomer-based secondary nucleation platforms, expanding the conceptual framework of prion assembly beyond fibril-end elongation alone.

biochemistry↗

bioRxiv2023

The smallest infectious substructure encoding the prion strain structural determinant revealed by spontaneous dissociation of misfolded prion protein assemblies

It is commonly accepted that the prion replicative propensity and strain structural determinant (SSD) are encoded in the fold of PrPSc amyloid fibril assemblies. By exploring the quaternary structure dynamicity of several prion strains, we revealed that all mammalian prion assemblies exhibit the generic property of spontaneously generating two sets of discreet infectious tetrameric and dimeric species differing significantly by their specific infectivity. By using perturbation approaches such as dilution and ionic strength variation, we demonstrated that these two oligomeric species were highly dynamic and evolved differently in the presence of chaotropic agents. In general, our observations of seven different prion strains from three distinct species highlight the high dynamicity of PrPSc assemblies as a common and intrinsic property of mammalian prions. The existence of such small infectious PrPSc species harboring the SSD indicates that the prion infectivity and the SSD are not restricted only to the amyloid fold but can also be encoded in other alternative quaternary structures. Such diversity in the quaternary structure of prion assemblies tends to indicate that the structure of PrPSc can be divided into two independent folding domains: a domain encoding the strain structural determinant and a second domain whose fold determines the type of quaternary structure that could adopt PrPSc assemblies. HighlightsO_LIMammalian prion assemblies are highly dynamic C_LIO_LIPrion assemblies spontaneously disassemble into two infectious oligomers C_LIO_LIPrion infectivity is not exclusively encoded in the amyloid fibrils structure C_LIO_LITwo independent folding domains could structure Prion assemblies C_LI

biochemistry↗