9BA1

Solution NMR structure of the human LETM1 F-EF-hand domain in the presence of calcium

9BA1 の概要

• エントリーDOI: 10.2210/pdb9ba1/pdb
• NMR情報: BMRB: 31155
• 分子名称: Mitochondrial proton/calcium exchanger protein, CALCIUM ION (2 entities in total)
• 機能のキーワード: ef-hand, f-ef-hand, letm1, mitochondrial, metal binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6821.77

構造登録者

Lin, Q.T.,Stathopulos, P.B. (登録日: 2024-04-03, 公開日: 2024-10-16, 最終更新日: 2024-11-27)

主引用文献

Lin, Q.T.,Colussi, D.M.,Lake, T.,Stathopulos, P.B.
An AI-informed NMR structure reveals an extraordinary LETM1 F-EF-hand domain that functions as a two-way regulator of mitochondrial calcium.
Structure, 32:2063-, 2024

PubMed Abstract: AlphaFold can accurately predict static protein structures but does not account for solvent conditions. Human leucine zipper EF-hand transmembrane protein-1 (LETM1) has one sequence-identifiable EF-hand but how calcium (Ca) affects structure and function remains enigmatic. Here, we used highly confident AlphaFold Cα predictions to guide nuclear Overhauser effect (NOE) assignments and structure calculation of the LETM1 EF-hand in the presence of Ca. The resultant NMR structure exposes pairing between a partial loop-helix and full helix-loop-helix, forming an unprecedented F-EF-hand with non-canonical Ca coordination but enhanced hydrophobicity for protein interactions compared to calmodulin. The structure also reveals the basis for pH sensing at the link between canonical and partial EF-hands. Functionally, mutations that augmented or weakened Ca binding increased or decreased matrix Ca, respectively, establishing F-EF as a two-way mitochondrial Ca regulator. Thus, we show how to synergize AI prediction with NMR data, elucidating a solution-specific and extraordinary LETM1 F-EF-hand.

PubMed: 39317198
DOI: 10.1016/j.str.2024.08.020

実験手法

SOLUTION NMR