Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Direct evidence of acid-driven protein desolvation
Δημιουργός/Συγγραφέας:	Hamdi, Farzad Skalidis, Ioannis Schwerin, Inken Kaja Belapure, Jaydeep Semchonok, Dmitry A Kyrilis, Fotis L Tüting, Christian Müller, Johannes Künze, Georg [EL] Καστρίτης, Παναγιώτης[EN] Kastritis, Panagiotis
Ημερομηνία:	2026-03-10
Γλώσσα:	Αγγλικά
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.2525949123
Άλλο:	41785322
Περίληψη:	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 pH-driven protein desolvation in 1974. Here, in a series of high-resolution cryoelectron microscopy structures of a protein complex at different pH values (from pH 9.0 to 3.5), we examined thousands of observable hydration sites. Cryoelectron microscopy data, in agreement with constant-pH molecular dynamics simulations, show that nearly half of protein-bound waters exchanged with the bulk solvent upon acidification, with ~100 waters lost per pH 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 pH conditions, accounting for 40% of resolved waters. Those waters displayed denser packing than less persistent waters, forming a pH-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.
Τίτλος πηγής δημοσίευσης:	Proceedings of the National Academy of Sciences of the United States of America
Τόμος/Κεφάλαιο:	123
Τεύχος:	10
Θεματική Κατηγορία:	[EL] Δομική Βιολογία[EN] Structural Biology [EL] Βιοχημεία[EN] Biochemistry [EL] Μοριακή Βιολογία[EN] Molecular Biology [EL] Φασματοσκοπία[EN] Spectroscopy
Λέξεις-Κλειδιά:	cryo-EM molecular dynamics protein hydration water molecules
Χρηματοδότης:	European Union European Union HORIZON-MSCA-2024-PF-01 Federal Ministry of Education and Research European Regional Development Funds (EFRE) Deutsche Forschungsgemeinschaft FCT—Fundação para a Ciência e a Tecnologia
Χρηματοδοτικό πρόγραμμα:	Horizon Europe ERA Chair “hot4cryo” Martin Luther University Halle-Wittenberg
Αναγνωριστικό χρηματοδοτικού προγράμματος:	101086665 101207412 03Z22HN23 03Z22HI2 03COV04 ZS/2016/04/78115 ZS/2024/05/187255 391498659 RTG 2467 514901783 SFB 1664 [A04, C04, and D01] UIDB/04612/2020 UIDP/04612/2020 LA/P/0087/2020
Κάτοχος πνευματικών δικαιωμάτων:	© 2026 the Author(s). Published by PNAS.
Όροι και προϋποθέσεις δικαιωμάτων:	This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.1073/pnas.2525949123
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο