Folding correction of ABC-transporter ABCB1 by pharmacological chaperones: a mechanistic concept.

ABSTRACT: Point mutations of ATP-binding cassette (ABC) proteins are a common cause of human diseases. Available crystal structures indicate a similarity in the architecture of several members of this protein family. Their molecular architecture makes these proteins vulnerable to mutation, when critical structural elements are affected. The latter preferentially involve the two transmembrane domain (TMD)/nucleotide-binding domain (NBD) interfaces (transmission interfaces), formation of which requires engagement of coupling helices of intracellular loops with NBDs. Both, formation of the active sites and engagement of the coupling helices, are contingent on correct positioning of ICLs 2 and 4 and thus an important prerequisite for proper folding. Here, we show that active site compounds are capable o

SUBMITTER: Spork M 

PROVIDER: S-EPMC5464349 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature