Combining NMR and small angle scattering in integrative structural biology - from molecular chaperones to splicing regulation

by Prof. Michael Sattler (Helmholtz Munich and TUM School of Natural Sciences, Department of Bioscience and Bavarian NMR Center,)

Monday 8 Jul 2024, 14:30 → 15:30 Europe/Berlin

PH HS 3 (Physics Department)

We combine solution NMR, X-ray crystallography, small angle X-ray/neutron scattering, and cryo-EM in integrative structural biology approaches to study the structure and dynamic conformations of multidomain (RNA-binding) proteins and protein complexes. These complexes play important roles in RNA-based gene regulation, cellular signalling and molecular chaperones. NMR is an important, versatile method to study molecular interactions and conformational dynamics of protein, RNAs and their complexes and can be readily combined with small angle scattering (SAXS/SANS) providing information about conformational dynamics, but also for refinement and validation of structural models predicted by deep learning methods, such as AlphaFold2. 

The lecture will highlight the combination of NMR and SAXS/SANS with examples from dynamic protein-RNA interactions, RNA structure and dynamic conformational states in molecular chaperones 

References 

• Martinez-Lumbreras S, Trager LK, Mulorz MM, Payr M, Dikaya V, Hipp C, Konig J, Sattler M Intramolecular autoinhibition regulates the selectivity of PRPF40A tandem WW domains for proline-rich motifs. (2024) Nat Commun 15, 3888. doi: 10.1038/s41467-024-48004-x 

• Delhommel F, Martinez-Lumbreras S, Sattler M Combining NMR, SAXS and SANS to characterize the structure and dynamics of protein complexes. (2023) Methods Enzymol 678, 263-297. doi: 10.1016/bs.mie.2022.09.020 

• Soni K, Jagtap PKA, Martinez-Lumbreras S, Bonnal S, Geerlof A, Stehle R, Simon B, Valcarcel J, Sattler M Structural basis for specific RNA recognition by the alternative splicing factor RBM5. (2023) Nat Commun 14, 4233; doi: 10.1038/s41467-023-39961-w 

• Lopez A, Dahiya V, Delhommel F, Freiburger L, Stehle R, Asami S, Rutz D, Blair L, Buchner J, Sattler M. Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network. (2021) Sci Adv 7. doi: 10.1126/sciadv.abl7295 

• Kooshapur H, Choudhury NR, Simon B, Muhlbauer M, Jussupow A, Fernandez N, Jones AN, Dallmann A, Gabel F, Camilloni C, Michlewski G, Caceres JF, Sattler M Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1. (2018) Nat Commun 9, 2479. doi: 10.1038/s41467-018-04871-9 

• Sonntag M, Jagtap PKA, Simon B, Appavou MS, Geerlof A, Stehle R, Gabel F, Hennig J, Sattler M Segmental, Domain-Selective Perdeuteration and Small-Angle Neutron Scattering for Structural Analysis of Multi-Domain Proteins. (2017) Angew Chem Int Ed Engl 56, 9322-9325. doi: 10.1002/anie.201702904