Biology subjects

Schwartz, C. L.

Publications and source records attributed to Schwartz, C. L..

4 recordsLinked to original sources

bioRxiv2024

pr-independent biogenesis of infectious mature Zika virus particles

Flavivirus assembly at the endoplasmic reticulum is driven by the structural proteins envelope (E) and premembrane (prM). Here, contrary to the established paradigm for flavivirus assembly, we demonstrate that the biogenesis of flavivirus particles does not require an intact prM nor proteolytic activation. The expression of E preceded by a truncated version of prM (M-E) was sufficient for the formation of non-infectious Zika virus subviral particles and pseudo-infectious reporter virions. Subviral particles encoded by a ZIKV M-E DNA vaccine elicited a neutralizing antibody response that was insensitive to the virion maturation state, a feature of flavivirus humoral immunity shown to correlate with protection. M-E vaccines that uniformly present structural features shared with mature virions offer a higher quality and broadly applicable approach to flavivirus vaccination.

microbiology↗

bioRxiv2022

Cryo-EM of prion strains from the same genotype of host identifies conformational determinants

Prion strains in a given type of mammalian host are distinguished by differences in clinical presentation, neuropathological lesions, survival time, and characteristics of the infecting prion protein (PrP) assemblies. Near-atomic structures of prions from two host species with different PrP sequences have been determined but comparisons of distinct prion strains of the same amino acid sequence are needed to identify purely conformational determinants of prion strain characteristics. Here we report a 3.2 [A] resolution cryogenic electron microscopy-based structure of the 22L prion strain purified from the brains of mice engineered to express only PrP lacking glycophosphatidylinositol anchors (a22L). Comparison of this near-atomic structure to our recently determined structure of the aRML strain propagated in the same inbred mouse reveals that these two mouse prion strains have distinct conformational templates for growth via incorporation of PrP molecules of the same sequence. Both a22L and aRML are assembled as stacks of PrP molecules forming parallel in-register intermolecular {beta}-sheets and intervening loops, with single monomers spanning the ordered fibril core. Each monomer shares an N-terminal steric zipper, three major {beta}-arches, and an overall V-shape, but the details of these and other conformational features differ markedly. Thus, variations in shared conformational motifs within a parallel in-register {beta}-stack fibril architecture provide a structural basis for prion strain differentiation within a single host genotype.

biophysics↗

bioRxiv2021

Structure of anchorless RML prion reveals motif variation between strains

Little is known about the structural basis of prion strains. Here we provide a high (3.0 [A]) resolution cryo-electron microscopy-based structure of brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register {beta}-sheet-based core. However, detailed comparisons reveal that variations in shared structural motifs provide a basis for prion strain determination. One-sentence summaryCryo-electron microscopy reveals a near-atomic structure of an infectious, brain-derived murine prion fibril and strain differences.

biochemistry↗

bioRxiv2016

Microtubules with a twist: a lumenal interrupted helix in human sperm tail microtubules

Eukaryotic flagella are complex cellular extensions involved in many human diseases gathered under the term ciliopathies. Currently, detailed insights on flagellar structure come from studies on protozoa. Here, cryo-electron tomography (cryo-ET) of intact human spermatozoon tails showed a variable number of microtubules in the singlet region. Inside their lumen, a novel left-handed interrupted helix which extends several micrometers at their plus ends was discovered. This structure was named Tail Axoneme Intra-Lumenal Spiral (TAILS) and binds directly to 11 protofilaments on the internal microtubule wall, coaxial with the surrounding microtubule lattice. It leaves a gap over the microtubule seam, which was directly visualized in both singlet and doublet microtubules. We suggest that TAILS may stabilize microtubules, enable rapid swimming or play a role in controlling the swimming direction of spermatozoa.

cell biology↗