9KVZ

Cryo-EM structure of SLC30A10 in the absence of Mn2+, determined in inward-facing conformation

Summary for 9KVZ

• Entry DOI: 10.2210/pdb9kvz/pdb
• EMDB information: 62605
• Descriptor: Calcium/manganese antiporter SLC30A10 (1 entity in total)
• Functional Keywords: manganese transpoter, slc30a10, znt10, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 105481.66

Authors

Yang, H.,Zhang, J.K.,Shen, X. (deposition date: 2024-12-05, release date: 2025-10-15)

Primary citation

Shen, X.,Zhang, J.K.,Sun, P.,Zhong, H.,He, R.,Wang, S.,Guo, X.,Yang, H.
Molecular mechanisms of SLC30A10-mediated manganese transport.
Nat Commun, 16:8581-8581, 2025

PubMed Abstract: Manganese ion (Mn²⁺) is crucial for various physiological processes, yet excessive levels disrupt cellular homeostasis and impair the function of multiple organelles. The transporter SLC30A10 plays a pivotal role in Mn²⁺ homeostasis by exporting Mn²⁺ from cells, preventing toxic effects. Mutations in the SLC30A10 gene result in Mn²⁺ accumulation and lead to disorders such as hypermanganesemia with dystonia 1 (HMNDYT1). Despite its physiological significance, the structural basis underlying Mn²⁺ binding and the detailed transport mechanisms of SLC30A10 remain unknown. Here, we present diverse conformations of high-resolution cryo-electron microscopy (cryo-EM) structures that reveal a Mn²⁺-binding site in SLC30A10, setting it apart from other SLC30 family transporters. Furthermore, we show that the HMNDYT1-associated D40A mutation interrupts Mn²⁺ binding and transport, identifying D40 as a potential therapeutic target. These findings provide structural insights into Mn²⁺ transport mechanisms mediated by SLC30A10, advancing our understanding of Mn²⁺ binding and potential targets for future therapeutic exploration.

PubMed: 41022720
DOI: 10.1038/s41467-025-63616-7

Experimental method

ELECTRON MICROSCOPY (2.94 Å)