6HD9

Crystal structure of the potassium channel MtTMEM175 with rubidium

Summary for 6HD9

• Entry DOI: 10.2210/pdb6hd9/pdb
• Related PRD ID: PRD_900001
• Descriptor: Nanobody,Maltose/maltodextrin-binding periplasmic protein, TMEM175, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: lysosome, tmem175, potassium channel, transport protein
• Biological source: Lama glama; More
• Total number of polymer chains: 2
• Total formula weight: 83686.36

Authors

Brunner, J.D.,Jakob, R.P.,Schulze, T.,Neldner, Y.,Moroni, A.,Thiel, G.,Maier, T.,Schenck, S. (deposition date: 2018-08-17, release date: 2019-08-28, Last modification date: 2024-01-17)

Primary citation

Brunner, J.D.,Jakob, R.P.,Schulze, T.,Neldner, Y.,Moroni, A.,Thiel, G.,Maier, T.,Schenck, S.
Structural basis for ion selectivity in TMEM175 K+channels.
Elife, 9:-, 2020

PubMed Abstract: The TMEM175 family constitutes recently discovered Kchannels that are important for autophagosome turnover and lysosomal pH regulation and are associated with the early onset of Parkinson Disease. TMEM175 channels lack a P-loop selectivity filter, a hallmark of all known K channels, raising the question how selectivity is achieved. Here, we report the X-ray structure of a closed bacterial TMEM175 channel in complex with a nanobody fusion-protein disclosing bound K ions. Our analysis revealed that a highly conserved layer of threonine residues in the pore conveys a basal K selectivity. An additional layer comprising two serines in human TMEM175 increases selectivity further and renders this channel sensitive to 4-aminopyridine and Zn. Our findings suggest that large hydrophobic side chains occlude the pore, forming a physical gate, and that channel opening by iris-like motions simultaneously relocates the gate and exposes the otherwise concealed selectivity filter to the pore lumen.

PubMed: 32267231
DOI: 10.7554/eLife.53683

Experimental method

X-RAY DIFFRACTION (3.5 Å)