A clinically relevant polymorphism in the Na⁺/taurocholate cotransporting polypeptide (NTCP) occurs at a rheostat position.

ABSTRACT: Conventionally, most amino acid substitutions at "important" protein positions are expected to abolish function. However, in several soluble-globular proteins, we identified a class of nonconserved positions for which various substitutions produced progressive functional changes; we consider these evolutionary "rheostats". Here, we report a strong rheostat position in the integral membrane protein, Na⁺/taurocholate (TCA) cotransporting polypeptide, at the site of a pharmacologically relevant polymorphism (S267F). Functional studies were performed for all 20 substitutions (S267X) with three substrates (TCA, estrone-3-sulfate, and rosuvastatin). The S267X set showed strong rheostatic effects on overall transport, and individual substitutions showed varied effects on transport kine

SUBMITTER: Ruggiero MJ 

PROVIDER: S-EPMC7948949 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature