4 research outputs found
Structural diversity of oligomeric beta-propellers with different numbers of identical bladders
β-Propellers arise through the amplification of a supersecondary structure element called a blade. This process produces toroids of between four and twelve repeats, which are almost always arranged sequentially in a single polypeptide chain. We found that new propellers evolve continuously by amplification from single blades. We therefore investigated whether such nascent propellers can fold as homo-oligomers before they have been fully amplified within a single chain. One- to six-bladed building blocks derived from two seven-bladed WD40 propellers yielded stable homo-oligomers with six to nine blades, depending on the size of the building block. High-resolution structures for tetramers of two blades, trimers of three blades, and dimers of four and five blades, respectively, show structurally diverse propellers and include a novel fold, highlighting the inherent flexibility of the WD40 blade. Our data support the hypothesis that subdomain-sized fragments can provide structural versatility in the evolution of new proteins
Molecular Basis for Transmission Barrier and Interference between Closely Related Prion Proteins in Yeast*
Replicating amyloids, called prions, are responsible for transmissible
neurodegenerative diseases in mammals and some heritable phenotypes in fungi.
The transmission of prions between species is usually inhibited, being highly
sensitive to small differences in amino acid sequence of the prion-forming
proteins. To understand the molecular basis of this prion interspecies barrier,
we studied the transmission of the
[PSI+] prion state from
Sup35 of Saccharomyces cerevisiae to hybrid Sup35 proteins with
prion-forming domains from four other closely related
Saccharomyces species. Whereas all the hybrid Sup35
proteins could adopt a prion form in S. cerevisiae, they could
not readily acquire the prion form from the
[PSI+] prion of S.
cerevisiae. Expression of the hybrid Sup35 proteins in S.
cerevisiae [PSI+]
cells often resulted in frequent loss of the native
[PSI+] prion. Furthermore,
all hybrid Sup35 proteins showed different patterns of interaction with the
native [PSI+] prion in terms of
co-polymerization, acquisition of the prion state, and induced prion loss, all
of which were also dependent on the
[PSI+] variant. The
observed loss of S. cerevisiae
[PSI+] can be related to
inhibition of prion polymerization of S. cerevisiae Sup35 and
formation of a non-heritable form of amyloid. We have therefore identified two
distinct molecular origins of prion transmission barriers between closely
sequence-related prion proteins: first, the inability of heterologous proteins
to co-aggregate with host prion polymers, and second, acquisition by these
proteins of a non-heritable amyloid fold