The noncanonical nucleotide binding site 1 of the bile salt export pump is optimized for proper function of the transporter.

Autor: Sohail I; Department of Zoology, Government College University Lahore, Lahore, Pakistan.; Institute of Medical Chemistry, Medical University of Vienna, Vienna, Austria., Hassan MU; Institute of Medical Chemistry, Medical University of Vienna, Vienna, Austria.; Institute of Industrial Biotechnology, Government College University Lahore, Lahore, Pakistan., Schmid D; Institute of Physiology, Medical University of Vienna, Vienna, Austria., Chiba P; Institute of Medical Chemistry, Medical University of Vienna, Vienna, Austria.
Jazyk: angličtina
Zdroj: Cell biology international [Cell Biol Int] 2024 May; Vol. 48 (5), pp. 638-646. Date of Electronic Publication: 2024 Feb 08.
DOI: 10.1002/cbin.12136
Abstrakt: The bile salt export pump (ABCB11/BSEP) is a hepatocyte plasma membrane-resident protein translocating bile salts into bile canaliculi. The sequence alignment of the four full-length transporters of the ABCB subfamily (ABCB1, ABCB4, ABCB5 and ABCB11) indicates that the NBD-NBD contact interface of ABCB11 differs from that of other members in only four residues. Notably, these are all located in the noncanonical nucleotide binding site 1 (NBS1). Substitution of all four deviant residues with canonical ones (quadruple mutant) significantly decreased the transport activity of the protein. In this study, we mutated two deviant residues in the signature sequence to generate a double mutant (R1221G/E1223Q). Furthermore, a triple mutant (E502S/R1221G/E1223Q) was generated, in which the deviant residues of the signature sequence and Q-loop were mutated concurrently to canonical residues. The double and triple mutants showed 80% and 60%, respectively, of the activity of wild-type BSEP. As expected, an increasing number of mutations gradually impair transport as an intricate network of interactions within the ABC proteins ensures proper functioning.
(© 2024 International Federation of Cell Biology.)
Databáze: MEDLINE
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