Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states
- 28 May 2013
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 110 (24), 9710-9715
- https://doi.org/10.1073/pnas.1217042110
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.This publication has 39 references indexed in Scilit:
- Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegansNature, 2012
- Specific Lipids Modulate the Transporter Associated with Antigen Processing (TAP)Online Journal of Public Health Informatics, 2011
- Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesisBlood, 2010
- ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acidsNucleic Acids Research, 2010
- Purification and Reconstitution of the Antigen Transport Complex TAPOnline Journal of Public Health Informatics, 2009
- Abcb10 physically interacts with mitoferrin-1 (Slc25a37) to enhance its stability and function in the erythroid mitochondriaProceedings of the National Academy of Sciences of the United States of America, 2009
- Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug BindingScience, 2009
- SUR1: a unique ATP-binding cassette protein that functions as an ion channel regulatorPhilosophical Transactions B, 2008
- Structure and mechanism of ATP-binding cassette transportersPhilosophical Transactions B, 2008
- Flexibility in the ABC transporter MsbA: Alternating access with a twistProceedings of the National Academy of Sciences of the United States of America, 2007