8ZMZ
Cryo-EM structure of R-eLACCO2 in the lactate-bound state
Summary for 8ZMZ
| Entry DOI | 10.2210/pdb8zmz/pdb |
| EMDB information | 60263 |
| Descriptor | Lactate-binding periplasmic protein TTHA0766,Red fluorescent protein drFP583, CALCIUM ION, (2S)-2-HYDROXYPROPANOIC ACID (3 entities in total) |
| Functional Keywords | fluorescent protein |
| Biological source | Thermus thermophilus HB8 More |
| Total number of polymer chains | 1 |
| Total formula weight | 70174.66 |
| Authors | Kamijo, Y.,Kusakizako, T.,Nureki, O.,Campbell, R.E.,Nasu, Y. (deposition date: 2024-05-24, release date: 2025-10-29, Last modification date: 2025-11-12) |
| Primary citation | Kamijo, Y.,Machler, P.,Ness, N.,Vu, C.Q.,Kusakizako, T.,Mannuthodikayil, J.,Ku, Z.,Boisvert, M.,Grebenik, E.,Miyazaki, I.,Hashizume, R.,Sato, H.,Liu, R.,Hori, Y.,Tomita, T.,Katayama, T.,Furube, A.,Caraveo, G.,Paquet, M.E.,Drobizhev, M.,Nureki, O.,Arai, S.,Brancaccio, M.,Campbell, R.E.,Kleinfeld, D.,Nasu, Y. A red fluorescent genetically encoded biosensor for in vivo imaging of extracellular L-lactate dynamics. Nat Commun, 16:9531-9531, 2025 Cited by PubMed Abstract: L-Lactate is increasingly recognized as an intercellular energy currency in mammals, but mysteries remain regarding the spatial and temporal dynamics of its release and uptake between cells via the extracellular environment. Here we introduce R-eLACCO2.1, a red fluorescent extracellular L-lactate biosensor that is superior to previously reported green fluorescent biosensors in in vivo sensitivity to increases in extracellular L-lactate and spectral orthogonality. R-eLACCO2.1 exhibits excellent fluorescence response in cultured cells, mouse brain slices, and live mice. R-eLACCO2.1 also serves as an effective fluorescence lifetime-based biosensor. Using R-eLACCO2.1, we monitor whisker stimulation and locomotion-induced changes in endogenous extracellular L-lactate in the somatosensory cortex of awake mice. To highlight the potential insights gained from in vivo measurements with R-eLACCO2.1, we perform dual-color imaging from the somatosensory cortex of actively locomoting mice. This enables us to simultaneously observe the neural activity, reported by a green fluorescent GCaMP calcium ion biosensor, and extracellular L-lactate. As the high-performance tool in the suite of extracellular L-lactate biosensors, R-eLACCO2.1 is ideally suited to delimit the emerging roles of L-lactate in mammalian metabolism. PubMed: 41162396DOI: 10.1038/s41467-025-64484-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.7 Å) |
Structure validation
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