8ZW8

Cryo-EM structure of trimethylamine transporter TmaT

8ZW8 の概要

• エントリーDOI: 10.2210/pdb8zw8/pdb
• EMDBエントリー: 60519
• 分子名称: Trimethylamine transporter (1 entity in total)
• 機能のキーワード: tma, electron transport
• 由来する生物種: Myroides profundi
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 179865.15

構造登録者

Chao, G. (登録日: 2024-06-12, 公開日: 2024-11-06, 最終更新日: 2025-07-16)

主引用文献

Gao, C.,Ding, H.T.,Li, K.,Cao, H.Y.,Wang, N.,Gu, Z.T.,Wang, Q.,Sun, M.L.,Chen, X.L.,Chen, Y.,Zhang, Y.Z.,Fu, H.H.,Li, C.Y.
Structural basis of a microbial trimethylamine transporter.
Mbio, 16:e0191424-e0191424, 2025

PubMed Abstract: Trimethylamine (TMA), a simple trace biogenic amine resulting from the decomposition of proteins and other macromolecules, is ubiquitous in nature. It is found in the human gut as well as in various terrestrial and marine ecosystems. While the role of TMA in promoting cardiovascular diseases and depolarizing olfactory sensory neurons in humans has only recently been explored, many microbes are well known for their ability to utilize TMA as a carbon, nitrogen, and energy source. Here, we report the first structure of a TMA transporter, TmaT, originally identified from a marine bacterium. TmaT is a member of the betaine-choline-carnitine transporter family, and we show that TmaT is an Na/TMA symporter, which possessed high specificity and binding affinity toward TMA. Furthermore, the structures of TmaT and two TmaT-TMA complexes were solved by cryo-EM. TmaT forms a homotrimer structure in solution. Each TmaT monomer has 12 transmembrane helices, and the TMA transport channel is formed by a four-helix bundle. TMA can move between different aromatic boxes, which provides the structural basis of TmaT importing TMA. When TMA is bound in location I, residues Trp146, Trp151, Tyr154, and Trp326 form an aromatic box to accommodate TMA. Moreover, Met105 also plays an important role in the binding of TMA. When TMA is transferred to location II, it is bound in the aromatic box formed by Trp325, Trp326, and Trp329. Based on our results, we proposed the TMA transport mechanism by TmaT. This study provides novel insights into TMA transport across biological membranes.

PubMed: 39576113
DOI: 10.1128/mbio.01914-24

実験手法

ELECTRON MICROSCOPY (3.05 Å)