Effect of pH on the Ability of N-Terminal Domain of Human NPC1 to Recognize, Bind, and Transfer Cholesterol.

ABSTRACT: Niemann-Pick type C1 (NPC1) is a large multidomain transmembrane protein essential for transporting cholesterol (CLR) from late endosomes and lysosomes to the endoplasmic reticulum and other cellular compartments. The lumen-facing N-terminal domain (NTD), involved in direct binding of CLR, is expected to have an optimum activity at acidic pH = 4.5. Here, we show that acidic pH is vital for the functionality of NPC1(NTD) and should be taken into account when studying the protein activity. We applied evolutionary, structural, and physicochemical analyses to decipher the consequences of a change in pH from acidic (pH = 4.5) to neutral (pH = 7.2) on the structural integrity of the NTD and its ability to bind CLR. We revealed that the change in pH from 4.5 to 7.2 increases the potential energy

SUBMITTER: Baker SM 

PROVIDER: S-EPMC7676335 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature