PROJECT #18501 RESEARCH FOR PARKINSONS
FOLDING PERFORMANCE PROFILE

PROJECT SUMMARY

Project 18500 is running wild-type Transmembrane Protein 175 (TMEM175).

Transmembrane Protein 175 (TMEM175) is a protein in the lysosomal membrane that functions as a "channel" for potassium ions to move between the open space in the cell (the cytoplasm) and the space within the lysosome (the lysosomal lumen).

TMEM175 is thought to play an important role in autophagy as a lysosomal protein, but its exact function in this process is not yet clear.

Nevertheless, dysfunction of TMEM175 is implicated in the development of Parkinson’s.

We know this because several mutational variants of TMEM175 have been identified in Parkinson’s patients, and experiments have shown that mice with these variants have some of the molecular and behavioral hallmarks of Parkinson’s.

An understanding of the fundamental mechanisms of TMEM175 will lead to new ways to discover drugs or therapeutic interventions to treat, prevent, or potentially even reverse Parkinson’s Disease. Project 18501 is the same as 18500 except that a histidine in the pore is modelled as neutral instead of positively charged (i.e.

it has one less proton).

We are testing to see if we need this as a way to bridge the open and closed states of the channel.

PROJECT INFO

Manager(s): Viktor Belay

Institution: Memorial Sloan Kettering Cancer Center

Project URL: viktor.belay@choderalab.org

PROJECT WORK UNIT SUMMARY

Atoms: 151,920

Core: 0x22

Status: Public