Architecture and Stoichiometry of Human Shelterin Using Single-Particle EM and Mass Analysis

Human shelterin is a six-subunit complex that binds telomeres, protects them from the DNA-damage response, and regulates the maintenance of telomeric DNA.

Although high-resolution structures have been generated for individual structured domains of shelterin subunits, the structure and stoichiometry of the full complex is unknown.

In this webinar, Dr. John Zinder, a Senior Scientist in the Structural Biology group at Odyssey Therapeutics, will discuss the purification of shelterin subcomplexes and reconstitution of the entire complex using full-length, recombinant subunits. By combining mass photometry, negative-stain electron microscopy (EM), crosslinking mass spectrometry (XLMS), AlphaFold modelling, and native mass spectrometry (MS), stoichiometries were obtained, as well as domain-scale architectures of shelterin subcomplexes.

In addition, Dr. Zinder will present data on shelterin complexes which feature extensive conformational heterogeneity, regardless of the presence of DNA substrates. He will also explain how shelterin adopts a multitude of conformations and its unusually high structural variability can be beneficial for its many functions at telomeres.

Key learning objectives

• Learn how to study conformational heterogeneity using single-particle mass analysis, including mass photometry
• Understand how modelling can aid in the characterization of highly flexible assemblies, such as shelterin
• Discover how mass photometry, especially when combined with complementary techniques, can be a powerful tool for determining the stoichiometry of a complex as well as its compositional heterogeneity at low concentrations

Who should attend?

• Anyone interested in mass photometry, the architecture of shelterin, protein complexes, protein-DNA interactions, telomere stability, structure determination, molecule prediction, homology modeling, and mass spectrometry.

Presenter: Davide Zinder PhD (Odyssey Therapeutics)

Dr. John Zinder is a Senior Scientist in the Structural Biology group at Odyssey Therapeutics and works in the development of novel therapeutics. He has an undergraduate degree in Chemistry from Cornell University, and a masters degree in Biochemistry from the University of Colorado. He was awarded a PhD in Chemical Biology from his research in Chris Lima’s lab at the Sloan Kettering Institute. Zinder subsequently became a Damon Runyon Postdoctoral Fellow in the de Lange and Walz labs at the Rockefeller University.

Presenter: Lawrence Howes (SelectScience)

Lawrence studied biological sciences at Swansea University, UK, before completing a master’s in epidemiology at the University of Bristol. As a member of the Editorial team, he now plays an integral role in shaping the content on SelectScience