9T44

Inward-open structure of a Zn2+-transporting P-type ATPase

Summary for 9T44

• Entry DOI: 10.2210/pdb9t44/pdb
• Descriptor: P-type Zn(2+) transporter (1 entity in total)
• Functional Keywords: p-type atpase, zinc transporter, e1 state, membrane protein
• Biological source: Mesorhizobium metallidurans
• Total number of polymer chains: 2
• Total formula weight: 189897.58

Authors

Lyu, P.,Longhin, E.,Wang, K.,Croll, T.,Bagenholm, V.,Gourdon, P. (deposition date: 2025-10-30, release date: 2026-11-04)

Primary citation

Lyu, P.,Longhin, E.,Sabzian-Molaei, F.,Montalvillo Ortega, F.,Li, P.,Wang, K.,Duelli, A.,Al-Jubair, T.,Ahmed Hotiana, H.,Ramos Becares, E.,Croll, T.,Meloni, G.,Andersson, M.,Bagenholm, V.,Gourdon, P.
Structural and functional insights into a Zn 2+ -transporting P-type ATPase.
Nat Commun, 17:-, 2026

PubMed Abstract: Zinc is essential for life yet toxic in excess, rendering homeostatic control vital for all organisms. Transition metal transporting P-type (P-) ATPase proteins are critical for this balance but remain poorly understood at the molecular level. Here, we present the inward-open structure of a dimeric zinc-transporting P-type ATPase, resolved at 3.6 Å resolution. Biochemical analyses and molecular dynamics simulations suggest that the N-terminal tail, harboring two so-called metal binding domains (MBDs), auto-inhibits the ATPase core and serves as a metal-sensitive sensor, releasing inhibition when intracellular metal levels rise. Contrary to the prevailing uptake models, the structure reveals an electronegatively charged uptake region that directly exposes a metal-binding cysteine of the invariant CPC-motif. We propose that a histidine-rich segment, positioned after the MBD closest to the core, donates ions to the CPC site. Consequently, an intricate interplay between the regulatory and ion-providing N-terminus and the ATPase core is present, safeguarding against zinc toxicity. Collectively, our findings shed light on the regulation and transport mechanism of P-ATPases, with implications for fundamental biology and the potential to inform future biotechnological and translational applications.

PubMed: 42894012
DOI: 10.1038/s41467-026-77558-1

Experimental method

X-RAY DIFFRACTION (3.58 Å)