Synthetic antibodies inhibit Bcl-2-associated X protein (BAX) through blockade of the N-terminal activation site

Journal of Biological Chemistry

Volumn 291, Issue 1, 2016, Pages 89-102

  Uchime, Onyinyechukwu ^a   Dai, Zhou ^b   Biris, Nikolaos ^a   Lee, David ^c   Sidhu, Sachdev S ^d   Li, Sheng ^c   Lai, Jonathan R ^b   Gavathiotis, Evripidis ^a  

^a ALBERT EINSTEIN CANCER CENTER   (United States)

^b ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODIES; BINDING SITES; BINS; CELL DEATH; CHEMICAL ACTIVATION; MASS SPECTROMETRY; MITOCHONDRIA; PROBES;

BCL-2 PROTEIN FAMILIES; CONFORMATIONAL CHANGE; HYDROGEN-DEUTERIUM EXCHANGE; LIPOSOMAL MEMBRANES; MITOCHONDRIAL APOPTOSIS; MITOCHONDRIAL TRANSLOCATION; POTENTIAL MECHANISM; SYNTHETIC ANTIBODY FRAGMENTS;

PROTEINS;

BH3 PROTEIN; CYTOCHROME C; PROTEIN BAX; PROTEIN BCL 2; ANTIBODY; IMMUNOGLOBULIN F(AB) FRAGMENT; LIPOSOME; MUTANT PROTEIN; PROTEIN BID;

AMINO TERMINAL SEQUENCE; APOPTOSIS; ARTICLE; CONFORMATIONAL TRANSITION; DEUTERIUM HYDROGEN EXCHANGE; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; INTERFEROMETRY; LIPOSOME MEMBRANE; MASS SPECTROMETRY; MITOCHONDRION; NUCLEAR MAGNETIC RESONANCE; OUTER MEMBRANE; PHAGE DISPLAY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FAMILY; PROTEIN INTERACTION; SIZE EXCLUSION CHROMATOGRAPHY; STOICHIOMETRY; AMINO ACID SEQUENCE; ANTAGONISTS AND INHIBITORS; BINDING SITE; CHEMISTRY; DRUG EFFECTS; METABOLISM; MITOCHONDRIAL MEMBRANE; MOLECULAR GENETICS; MOLECULAR MODEL; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PERMEABILITY; PROTEIN STABILITY; PROTEIN TRANSPORT;

AMINO ACID SEQUENCE; ANTIBODIES; APOPTOSIS; BCL-2-ASSOCIATED X PROTEIN; BH3 INTERACTING DOMAIN DEATH AGONIST PROTEIN; BINDING SITES; CYTOCHROMES C; HUMANS; IMMUNOGLOBULIN FAB FRAGMENTS; LIPOSOMES; MAGNETIC RESONANCE SPECTROSCOPY; MITOCHONDRIA; MITOCHONDRIAL MEMBRANES; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTANT PROTEINS; PERMEABILITY; PROTEIN STABILITY; PROTEIN TRANSPORT;

EID: 84952891730     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.680918     Document Type: Article

References (42)

1. Fuchs, Y., and Steller, H. (2011) Programmed cell death in animal development and disease. Cell 147, 742-758
2. Danial, N. N., and Korsmeyer, S. J. (2004) Cell death: critical control points. Cell 116, 205-219
3. Youle, R. J., and Strasser, A. (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 9, 47-59
4. Chipuk, J. E., Moldoveanu, T., Llambi, F., Parsons, M. J., and Green, D. R. (2010) The BCL-2 family reunion. Mol. Cell 37, 299-310
5. Hsu, Y. T., Wolter, K. G., and Youle, R. J. (1997) Cytosol-to-membrane redistribution of Bax and Bcl-X(L) during apoptosis. Proc. Natl. Acad. Sci. U.S.A. 94, 3668-3672
6. Wolter, K. G., Hsu, Y. T., Smith, C. L., Nechushtan, A., Xi, X. G., and Youle, R. J. (1997) Movement of Bax from the cytosol to mitochondria during apoptosis. J. Cell Biol. 139, 1281-1292
7. Walensky, L. D., and Gavathiotis, E. (2011) BAX unleashed: the biochemical transformation of an inactive cytosolic monomer into a toxic mitochondrial pore. Trends Biochem. Sci. 36, 642-652
8. Westphal, D., Kluck, R. M., and Dewson, G. (2014) Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis. Cell Death Differ. 21, 196-205
9. Suzuki, M., Youle, R. J., and Tjandra, N. (2000) Structure of Bax: coregulation of dimer formation and intracellular localization. Cell 103, 645-654
10. Gavathiotis, E., Suzuki, M., Davis, M. L., Pitter, K., Bird, G. H., Katz, S. G., Tu, H. C., Kim, H., Cheng, E. H., Tjandra, N., and Walensky, L. D. (2008) BAX activation is initiated at a novel interaction site. Nature 455, 1076-1081
11. Kim, H., Tu, H. C., Ren, D., Takeuchi, O., Jeffers, J. R., Zambetti, G. P., Hsieh, J. J., and Cheng, E. H. (2009) Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol. Cell 36, 487-499
12. Gavathiotis, E., Reyna, D. E., Davis, M. L., Bird, G. H., and Walensky, L. D. (2010) BH3-triggered structural reorganization drives the activation of proapoptotic BAX. Mol. Cell 40, 481-492
13. Gahl, R. F., He, Y., Yu, S., and Tjandra, N. (2014) Conformational rearrangements in the pro-apoptotic protein, Bax, as it inserts into mitochondria: a cellular death switch. J. Biol. Chem. 289, 32871-32882
14. Lovell, J. F., Billen, L. P., Bindner, S., Shamas-Din, A., Fradin, C., Leber, B., and Andrews, D. W. (2008) Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax. Cell 135, 1074-1084
15. Czabotar, P. E., Westphal, D., Dewson, G., Ma, S., Hockings, C., Fairlie, W. D., Lee, E. F., Yao, S., Robin, A. Y., Smith, B. J., Huang, D. C., Kluck, R. M., Adams, J. M., and Colman, P. M. (2013) Bax crystal structures reveal how BH3 domains activate Bax and nucleate its oligomerization to induce apoptosis. Cell 152, 519-531
16. Bleicken, S., Jeschke, G., Stegmueller, C., Salvador-Gallego, R., García- Sáez, A. J., and Bordignon, E. (2014) Structural model of active Bax at the membrane. Mol. Cell 56, 496-505
17. Sattler, M., Liang, H., Nettesheim, D., Meadows, R. P., Harlan, J. E., Eberstadt, M., Yoon, H. S., Shuker, S. B., Chang, B. S., Minn, A. J., Thompson, C. B., and Fesik, S. W. (1997) Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 275, 983-986
18. Ding, J., Zhang, Z., Roberts, G. J., Falcone, M., Miao, Y., Shao, Y., Zhang, X. C., Andrews, D. W., and Lin, J. (2010) Bcl-2 and Bax interact via the BH1-3 groove-BH3 motif interface and a novel interface involving the BH4 motif. J. Biol. Chem. 285, 28749-28763
19. Ding, J., Mooers, B. H., Zhang, Z., Kale, J., Falcone, D., McNichol, J., Huang, B., Zhang, X. C., Xing, C., Andrews, D. W., and Lin, J. (2014) After embedding in membranes antiapoptotic Bcl-XL protein binds both Bcl-2 homology region 3 and helix 1 of proapoptotic Bax protein to inhibit apoptotic mitochondrial permeabilization. J. Biol. Chem. 289, 11873-11896
20. Barclay, L. A., Wales, T. E., Garner, T. P., Wachter, F., Lee, S., Guerra, R. M., Stewart, M. L., Braun, C. R., Bird, G. H., Gavathiotis, E., Engen, J. R., and Walensky, L. D. (2015) Inhibition of Pro-apoptotic BAX by a noncanonical interaction mechanism. Mol. Cell 57, 873-886
21. Czabotar, P. E., Lessene, G., Strasser, A., and Adams, J. M. (2014) Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat. Rev. Mol. Cell Biol. 15, 49-63
22. Sidhu, S. S., and Fellouse, F. A. (2006) Synthetic therapeutic antibodies. Nat. Chem. Biol. 2, 682-688
23. Paduch, M., Koide, A., Uysal, S., Rizk, S. S., Koide, S., and Kossiakoff, A. A. (2013) Generating conformation-specific synthetic antibodies to trap proteins in selected functional states. Methods 60, 3-14
24. Fellouse, F. A., Esaki, K., Birtalan, S., Raptis, D., Cancasci, V. J., Koide, A., Jhurani, P., Vasser, M., Wiesmann, C., Kossiakoff, A. A., Koide, S., and Sidhu, S. S. (2007) High-throughput generation of synthetic antibodies from highly functional minimalist phage-displayed libraries. J. Mol. Biol. 373, 924-940
25. Koellhoffer, J. F., Chen, G., Sandesara, R. G., Bale, S., Saphire, E. O., Chandran, K., Sidhu, S. S., and Lai, J. R. (2012) Two synthetic antibodies that recognize and neutralize distinct proteolytic forms of the Ebola virus envelope glycoprotein. ChemBioChem 13, 2549-2557
26. Koerber, J. T., Thomsen, N. D., Hannigan, B. T., Degrado, W. F., and Wells, J. A. (2013) Nature-inspired design of motif-specific antibody scaffolds. Nat. Biotechnol. 31, 916-921
27. Gao, J., Sidhu, S. S., and Wells, J. A. (2009) Two-state selection of conformation- specific antibodies. Proc. Natl. Acad. Sci. U.S.A. 106, 3071-3076
28. Marsh, J. J., Guan, H. S., Li, S., Chiles, P. G., Tran, D., and Morris, T. A. (2013) Structural insights into fibrinogen dynamics using amide hydrogen/ deuterium exchange mass spectrometry. Biochemistry 52, 5491-5502
29. Li, S., Tsalkova, T., White, M. A., Mei, F. C., Liu, T., Wang, D., Woods, V. L., Jr., and Cheng, X. (2011) Mechanism of intracellular cAMP sensor Epac2 activation: cAMP-induced conformational changes identified by amide hydrogen/deuterium exchange mass spectrometry (DXMS). J. Biol. Chem. 286, 17889-17897
30. Zhang, Z., and Smith, D. L. (1993) Determination of amide hydrogen exchange by mass spectrometry: a new tool for protein structure elucidation. Protein Sci. 2, 522-531
31. de Vries, S. J., van Dijk, M., and Bonvin, A. M. (2010) TheHADDOCKweb server for data-driven biomolecular docking. Nat. Protoc. 5, 883-897
32. Marcatili, P., Olimpieri, P. P., Chailyan, A., and Tramontano, A. (2014) Antibody structural modeling with prediction of immunoglobulin structure (PIGS). Nat. Protoc. 9, 2771-2783
33. Morin, A., Eisenbraun, B., Key, J., Sanschagrin, P. C., Timony, M. A., Ottaviano, M., and Sliz, P. (2013) Collaboration gets the most out of software. eLife 2, e01456
34. Persson, H., Ye, W., Wernimont, A., Adams, J. J., Koide, A., Koide, S., Lam, R., and Sidhu, S. S. (2013) CDR-H3 diversity is not required for antigen recognition by synthetic antibodies. J. Mol. Biol. 425, 803-811
35. Yethon, J. A., Epand, R. F., Leber, B., Epand, R. M., and Andrews, D. W. (2003) Interaction with a membrane surface triggers a reversible conformational change in Bax normally associated with induction of apoptosis. J. Biol. Chem. 278, 48935-48941
36. Edwards, A. L., Gavathiotis, E., LaBelle, J. L., Braun, C. R., Opoku-Nsiah, K. A., Bird, G. H., and Walensky, L. D. (2013) Multimodal interaction with BCL-2 family proteins underlies the proapoptotic activity of PUMA BH3. Chem. Bio. 20, 888-902
37. Leshchiner, E. S., Braun, C. R., Bird, G. H., and Walensky, L. D. (2013) Direct activation of full-length proapoptotic BAK. Proc. Natl. Acad. Sci. U.S.A. 110, E986-995
38. Gavathiotis, E., Reyna, D. E., Bellairs, J. A., Leshchiner, E. S., and Walensky, L. D. (2012) Direct and selective small-molecule activation of proapoptotic BAX. Nat. Chem. Biol. 8, 639-645
39. Ma, J., Edlich, F., Bermejo, G. A., Norris, K. L., Youle, R. J., and Tjandra, N. (2012) Structural mechanism of Bax inhibition by cytomegalovirus protein vMIA. Proc. Natl. Acad. Sci. U.S.A. 109, 20901-20906
40. Dominguez, C., Boelens, R., and Bonvin, A. M. (2003) HADDOCK: a protein- protein docking approach based on biochemical or biophysical information. J. Am. Chem. Soc. 125, 1731-1737
41. Annis, M. G., Soucie, E. L., Dlugosz, P. J., Cruz-Aguado, J. A., Penn, L. Z., Leber, B., and Andrews, D. W. (2005) Bax forms multispanning monomers that oligomerize to permeabilize membranes during apoptosis. EMBO J. 24, 2096-2103
42. Tsai, C. J., Liu, S., Hung, C. L., Jhong, S. R., Sung, T. C., and Chiang, Y. W. (2015) BAX-induced apoptosis can be initiated through a conformational selection mechanism. Structure 23, 139-148