ABCMdb

PMID: 9841738

Jones PM, George AM
A new structural model for P-glycoprotein.
J Membr Biol. 1998 Nov 15;166(2):133-47., 1998-11-15 [PubMed]

Sentences

No. Mutations Sentence Comment

149 ABCB1 p.Thr209Cys ABCB1 p.Trp855Cys ABCB1 p.Gly211Cys ABCB1 p.Gly854Cys ABCB1 p.Ser850Cys Six substitutions on the putative extracellular loops between TMs 3 and 4 (T209C, G211C, T215C) and TMs 9 and 10 (S850C, G854C, W855C) unexpectedly failed to react with the labeling reagent. Login to comment 204 ABCB1 p.Leu975Cys ABCB1 p.Leu332Cys ABCB1 p.Gly346Cys ABCB1 p.Gly989Cys ABCB1 p.Pro350Cys ABCB1 p.Ser993Cys ABCB1 p.Phe343Cys ABCB1 p.Met986Cys Four cross-linked pairs, namely L332C/L975C, F343C/M986C, G346C/G989C and P350C/S993C, were generated in separate mutant molecules. Login to comment 207 ABCB1 p.Pro350Cys ABCB1 p.Ser993Cys Cross-linking of P350C to S993C severely impaired drug-stimulated ATPase activity, suggesting that the two regions of which they are components must be free to move independently for proper function. Login to comment 209 ABCB1 p.Leu975Cys ABCB1 p.Leu332Cys The cross-linking of the first pair (L332C/L975C) required the presence of ATP, was unaffected by drug substrates, and could not be reversed by treatment with dithiothreitol. Login to comment 211 ABCB1 p.Leu339Cys ABCB1 p.Val982Cys ABCB1 p.Phe336Cys ABCB1 p.Ser979Cys In contrast, two other potential pairs that lie between the first and second of the four cross-linked pairs within TMs 6 and 12 (Loo & Clarke, 1997), namely F336C/S979C and L339C/V982C, failed to form cross-links. Login to comment