8UBH
Solution NMR structure of KaiB variant from Thermosynechococcus elongatus vestitus (KaiBTV-4)
Summary for 8UBH
| Entry DOI | 10.2210/pdb8ubh/pdb |
| NMR Information | BMRB: 31107 |
| Descriptor | Circadian oscillation regulator (1 entity in total) |
| Functional Keywords | protein folding, metamorphic protein, fold-switching, signaling protein |
| Biological source | Thermosynechococcus vestitus BP-1 |
| Total number of polymer chains | 1 |
| Total formula weight | 9920.54 |
| Authors | Ojoawo, A.,Wayment-Steele, H.K.,Kern, D. (deposition date: 2023-09-23, release date: 2023-10-25, Last modification date: 2024-05-15) |
| Primary citation | Wayment-Steele, H.K.,Ojoawo, A.,Otten, R.,Apitz, J.M.,Pitsawong, W.,Homberger, M.,Ovchinnikov, S.,Colwell, L.,Kern, D. Predicting multiple conformations via sequence clustering and AlphaFold2. Nature, 625:832-839, 2024 Cited by PubMed Abstract: AlphaFold2 (ref. ) has revolutionized structural biology by accurately predicting single structures of proteins. However, a protein's biological function often depends on multiple conformational substates, and disease-causing point mutations often cause population changes within these substates. We demonstrate that clustering a multiple-sequence alignment by sequence similarity enables AlphaFold2 to sample alternative states of known metamorphic proteins with high confidence. Using this method, named AF-Cluster, we investigated the evolutionary distribution of predicted structures for the metamorphic protein KaiB and found that predictions of both conformations were distributed in clusters across the KaiB family. We used nuclear magnetic resonance spectroscopy to confirm an AF-Cluster prediction: a cyanobacteria KaiB variant is stabilized in the opposite state compared with the more widely studied variant. To test AF-Cluster's sensitivity to point mutations, we designed and experimentally verified a set of three mutations predicted to flip KaiB from Rhodobacter sphaeroides from the ground to the fold-switched state. Finally, screening for alternative states in protein families without known fold switching identified a putative alternative state for the oxidoreductase Mpt53 in Mycobacterium tuberculosis. Further development of such bioinformatic methods in tandem with experiments will probably have a considerable impact on predicting protein energy landscapes, essential for illuminating biological function. PubMed: 37956700DOI: 10.1038/s41586-023-06832-9 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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