Over The resolution revolution in cryo-electronenmicroscopy: seeing is believing

The resolution revolution in cryo-electronenmicroscopy: seeing is believing

Avondlezing georganiseerd door de Groningse Chemische Kring.

In the past few years, astonishing progress has been made in single particle cryo transmission electron microscopy (cryo-EM), which used to be limited to large complexes and low-resolution models. Until recently, X-ray crystallography and NMR spectroscopy were solely able to deliver the resolution necessary to describe a structure and understand the biological function of proteins at an atomic level – a perquisite of any structure-based drug design approach. However, recent advances in direct electron detection cameras, high-end microscopes and image processing have revolutionized the field entirely. This ‘resolution revolution’ translates into structures at atomic resolution (≥1.5 Å), even for small (64 kDa) and asymmetric proteins and has created a worldwide excitement for the method and was awarded with the 2017 Nobel Prize in Chemistry. Cryo-EM has thus become an indispensable technique for atomic structure determination, in particular for the pharmacological important membrane proteins, complementing X-ray crystallography while offering several advantages, namely it: (i) requires only small amounts of protein; (ii) is not limited by formation of protein crystals, which are often restricted to energetically favoured conformations; (iii) allows induction of conformational changes by rapid buffer exchange; (iv) permits the use of nanodiscs or lipid vesicles to mimic a native environment and resolves the micelle/bilayer; (v) enables determination of low and high-resolution structures; and (vi) is not hampered by sample compositional or conformational heterogeneity. As a result, cryo-EM allows us today to perform ground-breaking and in some cases unprecedented research.

Curriculum vitae
Cristina Paulino, originally from Portugal, studied biochemistry at the Heinrich-Heine University in Dusseldorf, Germany, graduating in 2008. During her undergraduate and following doctoral studies at the Max-Planck Institute of Biophysics in Frankfurt, Germany, she was trained in membrane protein biology. Under the supervision of Prof. Werner Kühlbrandt, a pioneer in the field, she became proficient in electron cryo-microscopy (cryo-EM) and obtained her PhD with distinction in 2014. Building upon her expertize, she established cryo-EM during her postdoctoral studies in the group of Prof. Raimund Dutzler (University of Zurich, Switzerland). In 2017 she obtained a tenure-tracked position as an Assistant Professor and head of the cryo-EM unit at the University of Groningen. Her interdisciplinary research combines structural data, determined by high-resolution single particle cryo-EM, with the functional characterisation of target proteins. Her main interest is focussed on elucidating the structure-function relationships that explain the transport mechanism of membrane transporters and channels.
Paulino was awarded with a PhD Fellowship from the Portuguese Science and Technology Foundation FCT, a Postdoc Fellowship from the University of Zurich, a Marie Skłodowska-Curie Individual Fellowships, a NWO Veni grant and a NWO Start-Up grant.

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