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Open AccessFeature PaperReview

Integrative Approaches in Structural Biology: A More Complete Picture from the Combination of Individual Techniques

1
Center for Magnetic Resonance (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino (FI), Italy
2
Department of Chemistry ‘Ugo Schiff’, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino (FI), Italy
3
NeCEN, Institute of Biology Leiden, Leiden University, Gorlaeus Gebouw, Einsteinweg 55, 2333 CC Leiden, The Netherlands
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(8), 370; https://doi.org/10.3390/biom9080370
Received: 19 July 2019 / Revised: 8 August 2019 / Accepted: 11 August 2019 / Published: 14 August 2019
With the recent technological and computational advancements, structural biology has begun to tackle more and more difficult questions, including complex biochemical pathways and transient interactions among macromolecules. This has demonstrated that, to approach the complexity of biology, one single technique is largely insufficient and unable to yield thorough answers, whereas integrated approaches have been more and more adopted with successful results. Traditional structural techniques (X-ray crystallography and Nuclear Magnetic Resonance (NMR)) and the emerging ones (cryo-electron microscopy (cryo-EM), Small Angle X-ray Scattering (SAXS)), together with molecular modeling, have pros and cons which very nicely complement one another. In this review, three examples of synergistic approaches chosen from our previous research will be revisited. The first shows how the joint use of both solution and solid-state NMR (SSNMR), X-ray crystallography, and cryo-EM is crucial to elucidate the structure of polyethylene glycol (PEG)ylated asparaginase, which would not be obtainable through any of the techniques taken alone. The second deals with the integrated use of NMR, X-ray crystallography, and SAXS in order to elucidate the catalytic mechanism of an enzyme that is based on the flexibility of the enzyme itself. The third one shows how it is possible to put together experimental data from X-ray crystallography and NMR restraints in order to refine a protein model in order to obtain a structure which simultaneously satisfies both experimental datasets and is therefore closer to the ‘real structure’. View Full-Text
Keywords: integrative structural biology; X-ray crystallography; solution NMR; SSNMR; SAXS; cryo-EM integrative structural biology; X-ray crystallography; solution NMR; SSNMR; SAXS; cryo-EM
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MDPI and ACS Style

Cerofolini, L.; Fragai, M.; Ravera, E.; Diebolder, C.A.; Renault, L.; Calderone, V. Integrative Approaches in Structural Biology: A More Complete Picture from the Combination of Individual Techniques. Biomolecules 2019, 9, 370.

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