ATP binding cassette (ABC) transporters play critical roles in maintaining sterol balance in higher eukaryotes. The ABCG5/ABCG8 heterodimer (G5G8) mediates excretion of neutral sterols in liver and intestines1,2,3,4,5. Mutations disrupting G5G8 cause sitosterolaemia, a disorder characterized by sterol accumulation and premature atherosclerosis. Here we use crystallization in lipid bilayers to determine the X-ray structure of human G5G8 in a nucleotide-free state at 3.9 Å resolution, generating the first atomic model of an ABC sterol transporter. The structure reveals a new transmembrane fold that is present in a large and functionally diverse superfamily of ABC transporters. The transmembrane domains are coupled to the nucleotide-binding sites by networks of interactions that differ between the active and inactive ATPases, reflecting the catalytic asymmetry of the transporter. The G5G8 structure provides a mechanistic framework for understanding sterol transport and the disruptive effects of mutations causing sitosterolaemia.
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Berge, K. E. et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290, 1771–1775 (2000)
Lee, M. H. et al. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nature Genet. 27, 79–83 (2001)
Lu, K. et al. Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Am. J. Hum. Genet. 69, 278–290 (2001)
Graf, G. A. et al. Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface. J. Clin. Invest. 110, 659–669 (2002)
Graf, G. A. et al. ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J. Biol. Chem. 278, 48275–48282 (2003)
Theodoulou, F. L. & Kerr, I. D. ABC transporter research: going strong 40 years on. Biochem. Soc. Trans. 43, 1033–1040 (2015)
Dean, M., Rzhetsky, A. & Allikmets, R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 11, 1156–1166 (2001)
Caffrey, M. Crystallizing membrane proteins for structure determination: use of lipidic mesophases. Annu. Rev. Biophys. 38, 29–51 (2009)
Rosenbaum, D. M. et al. GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 318, 1266–1273 (2007)
Lin, D. Y.-W., Huang, S. & Chen, J. Crystal structures of a polypeptide processing and secretion transporter. Nature 523, 425–430 (2015)
Chen, S., Oldham, M. L., Davidson, A. L. & Chen, J. Carbon catabolite repression of the maltose transporter revealed by X-ray crystallography. Nature 499, 364–368 (2013)
Johnson, B. J. H., Lee, J.-Y., Pickert, A. & Urbatsch, I. L. Bile acids stimulate ATP hydrolysis in the purified cholesterol transporter ABCG5/G8. Biochemistry 49, 3403–3411 (2010)
Faham, S. et al. Crystallization of bacteriorhodopsin from bicelle formulations at room temperature. Protein Sci. 14, 836–840 (2005)
Hohl, M., Briand, C., Grütter, M. G. & Seeger, M. A. Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation. Nature Struct. Mol. Biol. 19, 395–402 (2012)
Ward, A. B. et al. Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain. Proc. Natl Acad. Sci. USA 110, 13386–13391 (2013)
Hollenstein, K., Frei, D. C. & Locher, K. P. Structure of an ABC transporter in complex with its binding protein. Nature 446, 213–216 (2007)
Hvorup, R. N. et al. Asymmetry in the structure of the ABC transporter-binding protein complex BtuCD-BtuF. Science 317, 1387–1390 (2007)
Wang, F., Li, G., Gu, H.-M. & Zhang, D.-W. Characterization of the role of a highly conserved sequence in ATP binding cassette transporter G (ABCG) family in ABCG1 stability, oligomerization, and trafficking. Biochemistry 52, 9497–9509 (2013)
Yu, L. et al. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc. Natl Acad. Sci. USA 99, 16237–16242 (2002)
Hollenstein, K., Dawson, R. J. P. & Locher, K. P. Structure and mechanism of ABC transporter proteins. Curr. Opin. Struct. Biol. 17, 412–418 (2007)
Wang, J. et al. Sequences in the nonconsensus nucleotide-binding domain of ABCG5/ABCG8 required for sterol transport. J. Biol. Chem. 286, 7308–7314 (2011)
Oldham, M. L. & Chen, J. Crystal structure of the maltose transporter in a pretranslocation intermediate state. Science 332, 1202–1205 (2011)
Ovchinnikov, S., Kamisetty, H. & Baker, D. Robust and accurate prediction of residue-residue interactions across protein interfaces using evolutionary information. eLife 3, e02030 (2014)
Wang, B., Dukarevich, M., Sun, E. I., Yen, M. R. & Saier, M. H., Jr. Membrane porters of ATP-binding cassette transport systems are polyphyletic. J. Membr. Biol. 231, 1–10 (2009)
Ren, Q., Chen, K. & Paulsen, I. T. TransportDB: a comprehensive database resource for cytoplasmic membrane transport systems and outer membrane channels. Nucleic Acids Res. 35, D274–D279 (2007)
Frickey, T. & Lupas, A. CLANS: a Java application for visualizing protein families based on pairwise similarity. Bioinformatics 20, 3702–3704 (2004)
Morgan, T. H. Sex limited inheritance in Drosophila . Science 32, 120–122 (1910)
Webb, B. & Sali, A. Protein structure modeling with MODELLER. Methods Mol. Biol. 1137, 1–15 (2014)
Ewart, G. D., Cannell, D., Cox, G. B. & Howells, A. J. Mutational analysis of the traffic ATPase (ABC) transporters involved in uptake of eye pigment precursors in Drosophila melanogaster. Implications for structure-function relationships. J. Biol. Chem. 269, 10370–10377 (1994)
Mackenzie, S. M. et al. Mutations in the white gene of Drosophila melanogaster affecting ABC transporters that determine eye colouration. Biochim. Biophys. Acta 1419, 173–185 (1999)
Chloupková, M. et al. Expression of 25 human ABC transporters in the yeast Pichia pastoris and characterization of the purified ABCC3 ATPase activity. Biochemistry 46, 7992–8003 (2007)
Zhang, D.-W., Graf, G. A., Gerard, R. D., Cohen, J. C. & Hobbs, H. H. Functional asymmetry of nucleotide-binding domains in ABCG5 and ABCG8. J. Biol. Chem. 281, 4507–4516 (2006)
Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data. Methods Enzymol. 276, 307–326 (1997)
Minor, W., Cymborowski, M., Otwinowski, Z. & Chruszcz, M. HKL-3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes. Acta Crystallogr. D 62, 859–866 (2006)
Otwinowski, Z., Borek, D., Majewski, W. & Minor, W. Multiparametric scaling of diffraction intensities. Acta Crystallogr. A 59, 228–234 (2003)
Borek, D., Minor, W. & Otwinowski, Z. Measurement errors and their consequences in protein crystallography. Acta Crystallogr. D 59, 2031–2038 (2003)
Borek, D., Ginell, S. L., Cymborowski, M., Minor, W. & Otwinowski, Z. The many faces of radiation-induced changes. J. Synchrotron Radiat. 14, 24–33 (2007)
Borek, D., Cymborowski, M., Machius, M., Minor, W. & Otwinowski, Z. Diffraction data analysis in the presence of radiation damage. Acta Crystallogr. D 66, 426–436 (2010)
Borek, D., Dauter, Z. & Otwinowski, Z. Identification of patterns in diffraction intensities affected by radiation exposure. J. Synchrotron Radiat. 20, 37–48 (2013)
Sheldrick, G. M. Experimental phasing with SHELXC/D/E: combining chain tracing with density modification. Acta Crystallogr. D 66, 479–485 (2010)
Otwinowski, Z. Maximum likelihood refinement of heavy atom parameters. In Proc. CCP4 Study Weekend: Isomorphous Replacement and Anomalous Scattering (Eds Evans, P. R., Wolf, W., Leslie, A. G. W. ) 80–86 (Daresbury Laboratory: Science and Engineering Research Council, 1991)
Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D 67, 235–242 (2011)
Cowtan, K. & Main, P. Miscellaneous algorithms for density modification. Acta Crystallogr. D 54, 487–493 (1998)
Zhang, K. Y., Cowtan, K. & Main, P. Combining constraints for electron-density modification. Methods Enzymol. 277, 53–64 (1997)
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010)
Cowtan, K. The Buccaneer software for automated model building. 1. Tracing protein chains. Acta Crystallogr. D 62, 1002–1011 (2006)
Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53, 240–255 (1997)
Nicholls, R. A., Fischer, M., McNicholas, S. & Murshudov, G. N. Conformation-independent structural comparison of macromolecules with ProSMART. Acta Crystallogr. D 70, 2487–2499 (2014)
Davis, I. W. et al. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 35, W375–W383 (2007)
Chivian, D. et al. Prediction of CASP6 structures using automated Robetta protocols. Proteins 61 (Suppl. 7), 157–166 (2005)
Stone, D. K., Xie, X. S. & Racker, E. Inhibition of clathrin-coated vesicle acidification by duramycin. J. Biol. Chem. 259, 2701–2703 (1984)
Wang, J. et al. Relative roles of ABCG5/ABCG8 in liver and intestine. J. Lipid Res. 56, 319–330 (2015)
Kamisetty, H., Ovchinnikov, S. & Baker, D. Assessing the utility of coevolution-based residue-residue contact predictions in a sequence- and structure-rich era. Proc. Natl Acad. Sci. USA 110, 15674–15679 (2013)
Ovchinnikov, S. et al. Large-scale determination of previously unsolved protein structures using evolutionary information. eLife 4, e09248 (2015)
Vehlow, C. et al. CMView: interactive contact map visualization and analysis. Bioinformatics 27, 1573–1574 (2011)
Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926–935 (1983)
Bayly, C. I., Cieplak, P., Cornell, W. & Kollman, P. A. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model. J. Phys. Chem. 97, 10269–10280 (1993)
Case, D. A. et al. The Amber biomolecular simulation programs. J. Comput. Chem. 26, 1668–1688 (2005)
Wang, J., Wang, W., Kollman, P. A. & Case, D. A. Automatic atom type and bond type perception in molecular mechanical calculations. J. Mol. Graph. Model. 25, 247–260 (2006)
Wickstrom, L., Okur, A. & Simmerling, C. Evaluating the performance of the ff99SB force field based on NMR scalar coupling data. Biophys. J. 97, 853–856 (2009)
Dickson, C. J. et al. Lipid14: the amber lipid force field. J. Chem. Theory Comput. 10, 865–879 (2014)
Sagui, C., Pedersen, L. G. & Darden, T. A. Towards an accurate representation of electrostatics in classical force fields: efficient implementation of multipolar interactions in biomolecular simulations. J. Chem. Phys. 120, 73–87 (2004)
Ryckaert, J. P., Ciccotti, G. & Berendsen, H. Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J. Comput. Phys. 23, 321–341 (1977)
Uberuaga, B. P., Anghel, M. & Voter, A. F. Synchronization of trajectories in canonical molecular-dynamics simulations: observation, explanation, and exploitation. J. Chem. Phys. 120, 6363–6374 (2004)
Bahar, I., Lezon, T. R., Bakan, A. & Shrivastava, I. H. Normal mode analysis of biomolecular structures: functional mechanisms of membrane proteins. Chem. Rev. 110, 1463–1497 (2010)
Pei, J. & Grishin, N. V. PROMALS3D: multiple protein sequence alignment enhanced with evolutionary and three-dimensional structural information. Methods Mol. Biol. 1079, 263–271 (2014)
Katoh, K. & Standley, D. M. MAFFT: iterative refinement and additional methods. Methods Mol. Biol. 1079, 131–146 (2014)
Pei, J. & Grishin, N. V. AL2CO: calculation of positional conservation in a protein sequence alignment. Bioinformatics 17, 700–712 (2001)
Lazarevic, V. & Karamata, D. The tagGH operon of Bacillus subtilis 168 encodes a two-component ABC transporter involved in the metabolism of two wall teichoic acids. Mol. Microbiol. 16, 345–355 (1995)
Evans, I. J. & Downie, J. A. The nodI gene product of Rhizobium leguminosarum is closely related to ATP-binding bacterial transport proteins; nucleotide sequence analysis of the nodI and nodJ genes. Gene 43, 95–101 (1986)
Goldman, B. S., Beck, D. L., Monika, E. M. & Kranz, R. G. Transmembrane heme delivery systems. Proc. Natl Acad. Sci. USA 95, 5003–5008 (1998)
Ajdic´, D. et al. Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen. Proc. Natl Acad. Sci. USA 99, 14434–14439 (2002)
Han, C. S. et al. Pathogenomic sequence analysis of Bacillus cereus and Bacillus thuringiensis isolates closely related to Bacillus anthracis . J. Bacteriol. 188, 3382–3390 (2006)
We thank the University of Texas Southwestern Structural Biology Laboratory and the staff of the Advanced Photon Source (beamlines 19ID and 23ID) for support during data collection. We thank C. Zelasko, L. Donnelly, F. Xu, L. Nie, Z. Wang, Y. Ma, and C. Zhao for technical assistance. We also thank S. Wilkens for comments, and L. Rice, Y. Jiang, and R. Hibbs for providing reagents and equipment. This project was supported by grants from the American Heart Association South Central Affiliate- (0825285F; J.-Y.L.), the American Heart Association Texas Affiliate Beginning Grant-in-Aid (0463130Y; I.L.U.), the Welch Foundation (I-1770; D.M.R.), the Packard Foundation (D.M.R.), the Howard Hughes Medical Institute (H.H.H., N.V.G.), and the National Institutes of Health (HL72304 and P01-HL20948 (H.H.H., J.C.C., X.-S.X.), GM094575 (N.V.G.), GM053163 and GM117080 (Z.O.), and GM113050 (D.M.R.)). The Advanced Photon Source is a US Department of Energy Office of Science User Facility operated for the Department of Energy Office of Science by Argonne National Laboratory (DE-AC02-06CH11357).
The authors declare no competing financial interests.
Extended data figures and tables
a, G5G8 heterodimers were co-purified by sequential affinity chromatography (Ni-NTA and CBP) followed by gel-filtration chromatography using Superdex 200 (SD 200) as described in the Methods. Protein purity was analysed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) and Coomassie staining. b, Dimerization of detergent-soluble G5G8 was analysed by size fractionation using blue native PAGE (BN-PAGE) followed by Coomassie staining of the gel (top). Proteins were transferred to nitrocellulose and immunoblotting was performed using an anti-RGSH4 monoclonal antibody (Qiagen) and anti-G8 rabbit polyclonal antibodies (bottom). Arrows point to the G5G8 dimer. c, Bile acid stimulated ATPase activity of purified recombinant WT G5 and G8 (4 μg) and WT G5 and catalytic-deficient G8 (G8-G216D) (Mut, 8 μg). Each point represents the mean ± s.d. of three separate measurements.
Crystals of G5G8 were grown using bicelle crystallization (see Methods). Optimal diffraction-quality crystals were obtained by using cholesterol as additive to the bicelle matrices. Shown here are crystals observed under a light microscope without the polarizer. Scale bar, 100 μm. a, b, In the presence of 0–1% (mol) cholesterol, crystals grew up to 500 μm, but only diffracted to 7–10 Å. c, In the presence of 2–5% (mol) cholesterol, crystals grew to 50–150 μm (longest edge) and diffracted to 3.5–4 Å. d, A diffraction frame shows structural information of G5G8 crystals out beyond 3.9 Å resolution.
Extended Data Figure 3 Experimental electron density maps and crystal packing in G5G8 bicelle crystals.
a, Side view of Cα backbone for two G5G8 dimers in an asymmetric unit (containing two transporters) with the anomalous Fourier map calculated from W-clusters plotted at 3σ. b, Orthorhombic G5G8 bicelle crystals with lateral crystal packing of TMDs indicative of G5G8 reconstitution into phospholipid bilayers (G5: orange; G8: blue). c, Electron density maps (2Fo − Fc) show the complete G5G8 heterodimer (centre, contoured at 1.5σ), selected residues at the G5 ECD (upper left, 1.5σ), conserved three arginines of G5 (R198/R199/R200) in proximity to the Signature motif (bottom left, 1.0σ), R543 of G8 where point mutation R543S causes sitosterolaemia (upper right, 1.5σ), and Y432 on TMH5 (G5) and F561 on TMH5 (G8) at the TMD interface (bottom right, 1.5σ).
a, Sitosterolaemia mutation positions R419 (G5) and G574 (G8) at the G5-TMH2 and G8-TMH5 interface near the extracellular surface. b, Separation between the +4 glycine of G5 Walker A (G5, GSSGSGKT) and G8 Signature (LSGGE) motifs. c, Superposition of the nucleotide-free NBDs of TM287/288 (PDB accession number 4Q4H), BtuD (PDB accession number 2QI9), and Atm1 (PDB accession number 4MYC) with varying distances between NBDs. d, Left: surface-filled view of the NBDs of G5G8 showing contacts between the two half-transporters at the cytoplasmic apex. Middle: interaction between conserved NPFDF (G5) and NPADF (G8) sequences (grey dots). Right: closest distances between the two half-transporters.
a, b, Left: cartoon of G5G8 TMDs in transparent surface (orange and blue). Vestibules on opposing faces of the TMDs are highlighted in boxes. Middle: Fo − Fc difference electron density map contoured at 3.0σ showing extended features at the vestibules. TMHs are numbered. Right: highly conserved residues in G5 and G8 (sequence conservation ≥ 7, see Methods) are shown as orange (G5) and blue (G8) cartoon/sticks. c, Left: in vivo functional reconstitution assay using G5G8 KO mice (G5G8−/− mice)19. Biliary cholesterol levels from mice infected with RR (empty adenovirus), or with adenoviruses expressing human (h)G5:WT and hG8:WT, or with adenoviruses expressing hG5:A540F and hG8:WT are shown. Pictures of the bile are below the graph. Each experiment represents the mean ± s.d. from three infected mice (n = 3) in each group. Right: expression of hG5 and hG8 detected by immunoblotting using anti-hG5 monoclonal antibodies (see Methods). Connexin was used as the gel-loading control. As a positive control for the mouse and a negative control for the human anti-G5 antibody, we also immunoblotted liver membranes from G5G8+/− mice.
Extended Data Figure 6 TMD polar relay in other ABC transporters and molecular dynamics simulation of G5G8 structure.
a, b, Analysis of bacterial PCAT1 (a) and maltose transporter (MalK2EGF, b) structures reveals conserved polar residues in the TMD subunits. TMD superposition of a nucleotide-free structure with a nucleotide-bound structure shows breakage of hydrogen bonding in TMD polar relay (top right) and inward movement of coupling helices (bottom right). (Nucleotide-free PCAT1 (PDB accession number 4RY2), ATPγS-bound PCAT1 (PDB accession number 4s0f), nucleotide-free MalK2EGF (PDB accession number 3PV0), and ATP-bound MalK2EGF (PDB accession number 2R6G).) c, d, Molecular dynamics simulation (100 ns) and vibrational mode analysis performed on the nucleotide-free G5G8 structure (see Methods). For each vibrational mode, the contribution of each residue was calculated by adding up the vectors of the main chain atoms. Among the lowest 20 vibrational modes, modes 9 and 10 are shown. Mode 10 (c) describes collective movements (green-to-red vectors on the Cα atoms) between CpH/CnH/E-helix bundle and the interface at ATP-binding cassette, indicating inward movement of the CpH/CnH/E-helix bundles from both G5 and G8. This is consistent with stereotypical inward motion of coupling helices in bacterial ABC transporters. Mode 9 (d) describes a collective movement (arrows) of NBD (bottom) and TMH1, 3, and 4 in G8 (top), indicating coupling between NBD and TMD. R543 of G8, a conserved polar residue in the TMD polar relay where a disease-causing mutation occurs, is highlighted together with its interacting partner, E503.
a, Co-evolving residue pairs from the ABCG5 and ABCG8 TMD that were closer than an all-atom cutoff of 8 Å (≤8 Å) are depicted as lines connecting Cα atoms of the residues in contact in the respective TMD structures. b, Co-evolving pairs that are more spatially distant than the defined cutoff (>8 Å). Expanded views show potential interface contacts predicted by spatially distant G5 and G8 coevolving residue pairs (red lines connecting Cα atoms) (top). Cross contacts in G8 (red) were mapped from the distant G5 GREMLIN pairs near the interface (pink) using the GREMLIN MSA, and vice versa (bottom). For example, we mapped S538 from the predicted G5 pair L436/S538 to the corresponding residue in G8-Y567, and considered G5-L436 and G8-Y567 to be a potential interface contact. Predicted interface contacts that are distant in the nucleotide-free structure could form contacts at another stage of the ABCG ATPase cycle. c, Left: in vivo functional reconstitution assay using liver-specific G5G8−/− mice52. Biliary cholesterol levels of mice infected with RR (empty adenovirus), or with adenoviruses expressing hG5:WT and hG8:WT, or with adenoviruses expressing hG5:Y432A and hG8:WT are shown. G5-Y432 is part of the TMD polar relay and predicted to interact with G8-N568 during the sterol transport cycle (b). Each experiment represents the mean ± s.d. from three infected mice (n = 3) in each group. Right: immunoblot analysis of hG5 levels in membranes isolated from the mice using an anti-hG5 monoclonal antibody (see Methods). Connexin was used as the gel-loading control.
A model of the Drosophila melanogaster white/brown heterodimeric guanine pigment transporter was made using the program Modeller28. On the basis of the sequence alignment and comparison of scoring metrics for the two possible heterodimer models (that is, white modelled on G5 versus G8, brown on the other), we selected G8 (blue cartoon) as the white template and G5 (orange cartoon) as the brown template. At right, top/extracellular views of the G5G8 structure and white/brown model are shown, with residues important for dye interaction highlighted. At bottom is an MSA for the C-terminal region of TMH5, showing the conservation of the functionally important amino acids.
This file contains the uncropped gels and blots. (PDF 2453 kb)
This file contains Multiple sequence alignment (MSA) of ABCG5 (page 1) and ABCG8 (page 2). MSA of ABCG5 and ABCG8 subfamily members is colored by Jalview in bluescale according to identity. The sequences are labeled to the left according to the NCBI GI and accession number and numbers to the left and right correspond to the first and last residue number in the corresponding sequence line. The AL2CO conservation index for each position is mapped below the alignment. The first sequences are human ABCG5 (gi|11967969) and ABCG8 (gi|11967971). Top GREMLIN L/3 co-evolving residue pairs in the TMD of ABCG5 (pages 3-6) andABCG8 (pages 7-10). (PDF 8518 kb)
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Lee, JY., Kinch, L., Borek, D. et al. Crystal structure of the human sterol transporter ABCG5/ABCG8. Nature 533, 561–564 (2016). https://doi.org/10.1038/nature17666
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