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High-throughput Screening for Protein-based Inheritance in S. cerevisiae

High-throughput Screening for Protein-based Inheritance in S. cerevisiae

Published on: August 8, 2017

Molecular mechanisms for protein-encoded inheritance.

Jed J W Wiltzius¹, Meytal Landau, Rebecca Nelson

¹UCLA-DOE Institute for Genomics and Proteomics, Howard Hughes Medical Institute, Molecular Biology Institute, University of California, Los Angeles, California, USA.

Nature Structural & Molecular Biology

|August 18, 2009

Summary

Prion strains are encoded by protein conformations. New polymorphic crystal structures reveal two mechanisms: packing polymorphism and segmental polymorphism, explaining how these protein conformations endure transmission between cells and organisms.

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Area of Science:

Structural biology
Molecular biology
Prion disease research

Background:

Prion strains are phenotypic variants of prions, determined by protein conformations.
The stability and transmission mechanisms of these protein conformations between cells or organisms remain poorly understood.

Purpose of the Study:

To elucidate the structural mechanisms underlying prion strain encoding and transmission.
To investigate how protein conformations achieve stability for inter-cellular or inter-organismal transfer.

Main Methods:

Analysis of polymorphic crystal structures of prion and amyloid protein segments.
Identification of structural variations responsible for encoding prion strains.

Main Results:

Two novel structural mechanisms for prion strain encoding were identified: packing polymorphism and segmental polymorphism.
Packing polymorphism involves alternative arrangements of beta-sheets from the same protein segment.
Segmental polymorphism involves distinct beta-sheets formed by different protein segments.

Conclusions:

Polymorphic crystal structures provide molecular mechanisms for encoding prion strains.
Both packing and segmental polymorphism enable enduring protein conformations for strain encoding.
These protein-based information transfer mechanisms share similarities with nucleic acid-based mechanisms in microbial strain variation.