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Visualizing protein breathing motions associated with aromatic ring flipping.

Mariño Pérez L, Ielasi FS, Bessa LM, Maurin D, Kragelj J, Blackledge M, Salvi N, Bouvignies G, Palencia A, Jensen MR
Nature 602 695-700 (2022)
Related entries: 7nyk, 7nym, 7nyn, 7nyo, 7nzb, 7nzc, 7nzd

Cited: 12 times
EuropePMC logo PMID: 35173330

Abstract

Aromatic residues cluster in the core of folded proteins, where they stabilize the structure through multiple interactions. Nuclear magnetic resonance (NMR) studies in the 1970s showed that aromatic side chains can undergo ring flips-that is, 180° rotations-despite their role in maintaining the protein fold1-3. It was suggested that large-scale 'breathing' motions of the surrounding protein environment would be necessary to accommodate these ring flipping events1. However, the structural details of these motions have remained unclear. Here we uncover the structural rearrangements that accompany ring flipping of a buried tyrosine residue in an SH3 domain. Using NMR, we show that the tyrosine side chain flips to a low-populated, minor state and, through a proteome-wide sequence analysis, we design mutants that stabilize this state, which allows us to capture its high-resolution structure by X-ray crystallography. A void volume is generated around the tyrosine ring during the structural transition between the major and minor state, and this allows fast flipping to take place. Our results provide structural insights into the protein breathing motions that are associated with ring flipping. More generally, our study has implications for protein design and structure prediction by showing how the local protein environment influences amino acid side chain conformations and vice versa.

Articles - 7nyl mentioned but not cited (1)

  1. Visualizing protein breathing motions associated with aromatic ring flipping. Mariño Pérez L, Ielasi FS, Bessa LM, Maurin D, Kragelj J, Blackledge M, Salvi N, Bouvignies G, Palencia A, Jensen MR. Nature 602 695-700 (2022)


Reviews citing this publication (3)

  1. Scaffold proteins as dynamic integrators of biological processes. DiRusso CJ, Dashtiahangar M, Gilmore TD. J Biol Chem 298 102628 (2022)
  2. NMR Studies of Aromatic Ring Flips to Probe Conformational Fluctuations in Proteins. Akke M, Weininger U. J Phys Chem B 127 591-599 (2023)
  3. Specific isotopic labelling and reverse labelling for protein NMR spectroscopy: using metabolic precursors in sample preparation. Rowlinson B, Crublet E, Kerfah R, Plevin MJ. Biochem Soc Trans 50 1555-1567 (2022)

Articles citing this publication (8)

  1. Aromatic ring flips in differently packed ubiquitin protein crystals from MAS NMR and MD. Gauto DF, Lebedenko OO, Becker LM, Ayala I, Lichtenecker R, Skrynnikov NR, Schanda P. J Struct Biol X 7 100079 (2023)
  2. Characterizing Fast Conformational Exchange of Aromatic Rings Using Residual Dipolar Couplings: Distinguishing Jumplike Flips from Other Exchange Mechanisms. Dreydoppel M, Akke M, Weininger U. J Phys Chem B 126 7950-7956 (2022)
  3. Effect of Cross-Seeding of Wild-Type Amyloid-β1-40 Peptides with Post-translationally Modified Fibrils on Internal Dynamics of the Fibrils Using Deuterium Solid-State NMR. Rodgers A, Sawaged M, Ostrovsky D, Vugmeyster L. J Phys Chem B 127 2887-2899 (2023)
  4. Intrinsic structural dynamics dictate enzymatic activity and inhibition. Shukla VK, Siemons L, Hansen DF. Proc Natl Acad Sci U S A 120 e2310910120 (2023)
  5. Changes in the hydrophobic network of the FliGMC domain induce rotational switching of the flagellar motor. Nishikino T, Hijikata A, Kojima S, Shirai T, Kainosho M, Homma M, Miyanoiri Y. iScience 26 107320 (2023)
  6. Deciphering Evolutionary Trajectories of Lactate Dehydrogenases Provides New Insights into Allostery. Robin AY, Brochier-Armanet C, Bertrand Q, Barette C, Girard E, Madern D. Mol Biol Evol 40 msad223 (2023)
  7. Global insights into the fine tuning of human A2AAR conformational dynamics in a ternary complex with an engineered G protein viewed by NMR. Ferré G, Anazia K, Silva LO, Thakur N, Ray AP, Eddy MT. Cell Rep 41 111844 (2022)
  8. Protein Conformational Space at the Edge of Allostery: Turning a Nonallosteric Malate Dehydrogenase into an "Allosterized" Enzyme Using Evolution-Guided Punctual Mutations. Iorio A, Brochier-Armanet C, Mas C, Sterpone F, Madern D. Mol Biol Evol 39 msac186 (2022)


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