9SJU
Cryo-EM structure of Human Apoferritin at pH 7
Summary for 9SJU
| Entry DOI | 10.2210/pdb9sju/pdb |
| EMDB information | 54954 |
| Descriptor | Ferritin heavy chain, N-terminally processed, FE (III) ION, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | apoferritin, ferritin, metal storage, low ph, metal binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 24 |
| Total formula weight | 486162.00 |
| Authors | Skalidis, I.,Semchonok, D.A.,Tueting, C.,Hamdi, F.,Kastritis, P.L. (deposition date: 2025-09-01, release date: 2026-02-25, Last modification date: 2026-03-18) |
| Primary citation | Hamdi, F.,Skalidis, I.,Schwerin, I.K.,Belapure, J.,Semchonok, D.A.,Kyrilis, F.L.,Tuting, C.,Muller, J.,Kunze, G.,Kastritis, P.L. Direct evidence of acid-driven protein desolvation. Proc.Natl.Acad.Sci.USA, 123:e2525949123-e2525949123, 2026 Cited by PubMed Abstract: Water and its ability to modulate the protonation states of biomolecules govern the physical chemistry of life, dictating their metabolic functions. However, how amino acid protonation alters protein hydration and solubility is an open question since Kuntz and Kauzmann proposed p-driven protein desolvation in 1974. Here, in a series of high-resolution cryoelectron microscopy structures of a protein complex at different p values (from p 9.0 to 3.5), we examined thousands of observable hydration sites. Cryoelectron microscopy data, in agreement with constant-p molecular dynamics simulations, show that nearly half of protein-bound waters exchanged with the bulk solvent upon acidification, with ~100 waters lost per p unit per molecule. The loss of waters was most significant around the side chains of glutamate and aspartate residues while specific polar residues, mostly asparagine, anchored persistent waters. A positionally conserved hydration layer was observed across all p conditions, accounting for 40% of resolved waters. Those waters displayed denser packing than less persistent waters, forming a p-independent solvation shell. Acid-induced water exchange also displaced bound iron, providing a mechanistic link between solvation and metal release. Our findings demonstrate the core principles of acid-driven protein desolvation, resolving a 50-y-old biochemical hypothesis. PubMed: 41785322DOI: 10.1073/pnas.2525949123 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.08 Å) |
Structure validation
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