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Investigating the domain motions of an asymmetric ABC transporter (997.1)
Author(s) -
Tieleman Peter,
Corradi Valentina,
Singh Gurpreet,
Seeger Markus
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.997.1
Subject(s) - atp binding cassette transporter , atp hydrolysis , binding site , transmembrane domain , transporter , nucleotide , atpase , cyclic nucleotide binding domain , chemistry , walker motifs , biochemistry , biophysics , biology , membrane , enzyme , gene
ATP‐binding cassette (ABC) transporters transport lipids, sterols, peptides, toxins, nutrients, drugs and ions across membranes and consist of two transmembrane domains (TMDs) and two nucleotide‐binding domains (NBDs). Asymmetric ABC transporters feature specific mutations in one of the two ATP‐binding sites (the degenerate site), resulting in a reduced ATPase activity compared to the non‐mutated site (the consensus site). It has been proposed that in asymmetric ABC transporters ATP remains bound at the degenerate site, while ATP‐binding and ‐hydrolysis at the consensus site drive the transport cycle. Here, we investigate the effects of ATP‐binding and domains' motions of the heterodimeric transporter TM287/288 (Hohl et al., Nat. Struct. Mol. Biol. 2012). We have performed molecular dynamics (MD) simulations, for a total simulation time of ca. 10 microseconds, on the structure of TM287/288 in different nucleotide‐bound states. Our results show that in the absence of ATP at the consensus site, the simulation systems with and without ATP at the degenerate site do not completely dissociate at the NBD level, but reach an intermediate state in which contacts between the NBDs are still observed.