Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states

Shintre, C.A., Pike, A.C.W., Li, Q., Kim, J.I., Barr, A.J., Goubin, S., Shrestha, L., Yang, J., Berridge, G., Ross, J., Stansfeld, P.J., Sansom, M.S.P., Edwards, A.M., Bountra, C., Marsden, B., von Delft, F., Bullock, A.N., Gileadi, O., Burgess-Brown, N.A. and Carpenter, E.P. 2013. Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states. Proceedings of the National Academy of Sciences. 110 (24), pp. 9710-9715.

TitleStructures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states
AuthorsShintre, C.A., Pike, A.C.W., Li, Q., Kim, J.I., Barr, A.J., Goubin, S., Shrestha, L., Yang, J., Berridge, G., Ross, J., Stansfeld, P.J., Sansom, M.S.P., Edwards, A.M., Bountra, C., Marsden, B., von Delft, F., Bullock, A.N., Gileadi, O., Burgess-Brown, N.A. and Carpenter, E.P.
Abstract

ABCB10 is one of the three ATP-binding cassette (ABC) transporters found in the inner membrane of mitochondria. In mammals ABCB10 is essential for erythropoiesis, and for protection of mitochondria against oxidative stress. ABCB10 is therefore a potential therapeutic target for diseases in which increased mitochondrial reactive oxygen species production and oxidative stress play a major role. The crystal structure of apo-ABCB10 shows a classic exporter fold ABC transporter structure, in an open-inwards conformation, ready to bind the substrate or nucleotide from the inner mitochondrial matrix or membrane. Unexpectedly, however, ABCB10 adopts an open-inwards conformation when complexed with nonhydrolysable ATP analogs, in contrast to other transporter structures which adopt an open-outwards conformation in complex with ATP. The three complexes of ABCB10/ATP analogs reported here showed varying degrees of opening of the transport substrate binding site, indicating that in this conformation there is some flexibility between the two halves of the protein. These structures suggest that the observed plasticity, together with a portal between two helices in the transmembrane region of ABCB10, assist transport substrate entry into the substrate binding cavity. These structures indicate that ABC transporters may exist in an open-inwards conformation when nucleotide is bound. We discuss ways in which this observation can be aligned with the current views on mechanisms of ABC transporters.

JournalProceedings of the National Academy of Sciences
Journal citation110 (24), pp. 9710-9715
ISSN0027-8424
Year11 Jun 2013
PublisherNational Academy of Sciences
Digital Object Identifier (DOI)doi:10.1073/pnas.1217042110
Publication dates
Published11 Jun 2013

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