7NYN
Mutant Y526A of SH3 domain of JNK-interacting Protein 1 (JIP1)
This is a non-PDB format compatible entry.
Summary for 7NYN
| Entry DOI | 10.2210/pdb7nyn/pdb |
| Descriptor | SH3 domain of JNK-interacting Protein 1 (JIP1), PHOSPHATE ION, PENTAETHYLENE GLYCOL, ... (8 entities in total) |
| Functional Keywords | sh3 domain of jnk-interacting protein 1 (jip1), signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 12 |
| Total formula weight | 93596.61 |
| Authors | Perez, L.M.,Ielasi, F.S.,Palencia, A.,Jensen, M.R. (deposition date: 2021-03-23, release date: 2021-12-22, Last modification date: 2024-01-31) |
| Primary citation | Marino Perez, L.,Ielasi, F.S.,Bessa, L.M.,Maurin, D.,Kragelj, J.,Blackledge, M.,Salvi, N.,Bouvignies, G.,Palencia, A.,Jensen, M.R. Visualizing protein breathing motions associated with aromatic ring flipping. Nature, 602:695-700, 2022 Cited by PubMed 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 fold. It was suggested that large-scale 'breathing' motions of the surrounding protein environment would be necessary to accommodate these ring flipping events. 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. PubMed: 35173330DOI: 10.1038/s41586-022-04417-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.537 Å) |
Structure validation
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