Abstract
Historically proteins that form highly polymeric and filamentous assemblies have been notoriously difficult to study using high resolution structural techniques. This has been due to several factors that include structural heterogeneity, their large molecular mass, and available yields. However, over the past decade we are now seeing a major shift towards atomic resolution insight and the study of more complex heterogenous samples and in situ/ex vivo examination of multi-subunit complexes. Although supported by developments in solid state nuclear magnetic resonance spectroscopy (ssNMR) and computational approaches, this has primarily been due to advances in cryogenic electron microscopy (cryo-EM). The study of eukaryotic microtubules and bacterial pili are good examples, and in this review, we will give an overview of the technical innovations that have enabled this transition and highlight the advancements that have been made for these two systems. Looking to the future we will also describe systems that remain difficult to study and where further technical breakthroughs are required.
Highlights
In the 1930s-1950s, X-ray fibre diffraction studies of filamentous proteins by pioneers such as William Astbury, Francis Crick and Linus Pauling, laid the foundation for modern structural biology (Astbury and Street, 1932; Pauling and Corey, 1951a; Pauling and Corey, 1951b; Crick, 1952)
In the 1980s the first soluble protein was determined by solution state nuclear magnetic resonance (NMR) spectroscopy (Williamson et al, 1985) and with the development of recombinant protein expression systems (Itakura et al, 1977; Smith et al, 1983; Cregg et al, 1993), by the mid-1990s there became a clear exponential rise in soluble/globular macromolecular structures being deposited in the protein data bank (Berman et al, 2000)
Using solution NMR and X-ray crystallography we have gained significant understanding of filamentous systems through studying their lower-order subunits, due to technical limitations of these techniques, there has been a lack in our understanding of how these components interact and how this relates to their function
Summary
In the 1930s-1950s, X-ray fibre diffraction studies of filamentous proteins by pioneers such as William Astbury, Francis Crick and Linus Pauling, laid the foundation for modern structural biology (Astbury and Street, 1932; Pauling and Corey, 1951a; Pauling and Corey, 1951b; Crick, 1952). These early studies provided new insights into the structural properties of fibrous substances such as keratin and collagen, they could only offer global information.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
