Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin

Ultsch, Mark; Li, Bing; Maurer, Till; Mathieu, Mary; Adolfsson, Oskar; Muhs, Andreas; Pfeifer, Andrea; Pihlgren, Maria; Bainbridge, Travis W.; Reichelt, Mike; Ernst, James A.; Eigenbrot, Charles; Fuh, Germaine; Atwal, Jasvinder K.; Watts, Ryan J.; Wang, Weiru

doi:10.1038/srep39374

Title: Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin

Journal Article · Tue Dec 20 00:00:00 EST 2016 · Scientific Reports

DOI:https://doi.org/10.1038/srep39374· OSTI ID:1624879

Ultsch, Mark ^[1]; Li, Bing ^[1]; Maurer, Till ^[1]; Mathieu, Mary ^[1]; Adolfsson, Oskar ^[2]; Muhs, Andreas ^[2]; Pfeifer, Andrea ^[2]; Pihlgren, Maria ^[2]; Bainbridge, Travis W. ^[1]; Reichelt, Mike ^[1]; Ernst, James A. ^[1]; Eigenbrot, Charles ^[1]; Fuh, Germaine ^[1]; Atwal, Jasvinder K. ^[1]; Watts, Ryan J. ^[1]; Wang, Weiru ^[1]

Genentech, Inc., South San Francisco, CA (United States)
AC Immune SA, Lausanne (Switzerland)

Accumulation of amyloid-β (Aβ) peptides and amyloid plaque deposition in brain is postulated as a cause of Alzheimer’s disease (AD). The precise pathological species of Aβ remains elusive although evidence suggests soluble oligomers may be primarily responsible for neurotoxicity. Crenezumab is a humanized anti-Aβ monoclonal IgG4 that binds multiple forms of Aβ, with higher affinity for aggregated forms, and that blocks Aβ aggregation, and promotes disaggregation. To understand the structural basis for this binding profile and activity, we determined the crystal structure of crenezumab in complex with Aβ. The structure reveals a sequential epitope and conformational requirements for epitope recognition, which include a subtle but critical element that is likely the basis for crenezumab’s versatile binding profile. We find interactions consistent with high affinity for multiple forms of Aβ, particularly oligomers. Of note, crenezumab also sequesters the hydrophobic core of Aβ and breaks an essential salt-bridge characteristic of the β-hairpin conformation, eliminating features characteristic of the basic organization in Aβ oligomers and fibrils, and explains crenezumab’s inhibition of aggregation and promotion of disaggregation. These insights highlight crenezumab’s unique mechanism of action, particularly regarding Aβ oligomers, and provide a strong rationale for the evaluation of crenezumab as a potential AD therapy.

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Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1624879

Journal Information:: Scientific Reports, Vol. 6, Issue 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 66 works

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References (51)

Shape Complementarity at Protein/Protein Interfaces Lawrence, Michael C.; Colman, Peter M. Journal of Molecular Biology, Vol. 234, Issue 4 https://doi.org/10.1006/jmbi.1993.1648	journal	December 1993
Identification of Physiological and Toxic Conformations in Aβ42 Aggregates Masuda, Yuichi; Uemura, Satoko; Ohashi, Ryutaro ChemBioChem, Vol. 10, Issue 2 https://doi.org/10.1002/cbic.200800411	journal	January 2009
Isolation of Low-Molecular-Weight Proteins from Amyloid Plaque Fibers in Alzheimer's Disease Selkoe, Dennis J.; Abraham, Carmela R.; Podlisny, Marcia B. Journal of Neurochemistry, Vol. 46, Issue 6 https://doi.org/10.1111/j.1471-4159.1986.tb08501.x	journal	June 1986
Structure of aggregates revealed Tycko, Robert Nature, Vol. 537, Issue 7621 https://doi.org/10.1038/nature19470	journal	September 2016
X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross-beta conformation. Kirschner, D. A.; Abraham, C.; Selkoe, D. J. Proceedings of the National Academy of Sciences, Vol. 83, Issue 2 https://doi.org/10.1073/pnas.83.2.503	journal	January 1986
Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation Miles, Luke A.; Crespi, Gabriela A. N.; Doughty, Larissa Scientific Reports, Vol. 3, Issue 1 https://doi.org/10.1038/srep01302	journal	February 2013
Refinement of Macromolecular Structures by the Maximum-Likelihood Method Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3 https://doi.org/10.1107/S0907444996012255	journal	May 1997
Atomic-resolution dynamics on the surface of amyloid-β protofibrils probed by solution NMR Fawzi, Nicolas L.; Ying, Jinfa; Ghirlando, Rodolfo Nature, Vol. 480, Issue 7376 https://doi.org/10.1038/nature10577	journal	October 2011
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
The Essential Role of Soluble Aβ Oligomers in Alzheimer’s Disease Wang, Zi-Xuan; Tan, Lan; Liu, Jinyuan Molecular Neurobiology, Vol. 53, Issue 3 https://doi.org/10.1007/s12035-015-9143-0	journal	April 2015
Aβ40-Lactam(D23/K28) Models a Conformation Highly Favorable for Nucleation of Amyloid ^† Sciarretta, Kimberly L.; Gordon, David J.; Petkova, Aneta T. Biochemistry, Vol. 44, Issue 16 https://doi.org/10.1021/bi0474867	journal	April 2005
Molecular structural basis for polymorphism in Alzheimer's -amyloid fibrils Paravastu, A. K.; Leapman, R. D.; Yau, W. -M. Proceedings of the National Academy of Sciences, Vol. 105, Issue 47 https://doi.org/10.1073/pnas.0806270105	journal	November 2008
Passive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets? Moreth, Jens; Mavoungou, Chrystelle; Schindowski, Katharina Immunity & Ageing, Vol. 10, Issue 1 https://doi.org/10.1186/1742-4933-10-18	journal	January 2013
3D structure of Alzheimer's amyloid- (1-42) fibrils Luhrs, T.; Ritter, C.; Adrian, M. Proceedings of the National Academy of Sciences, Vol. 102, Issue 48 https://doi.org/10.1073/pnas.0506723102	journal	November 2005
Structural Basis of C-terminal β-Amyloid Peptide Binding by the Antibody Ponezumab for the Treatment of Alzheimer's Disease La Porte, Sherry L.; Bollini, Sangeetha Subbarao; Lanz, Thomas A. Journal of Molecular Biology, Vol. 421, Issue 4-5 https://doi.org/10.1016/j.jmb.2011.11.047	journal	August 2012
Atomic Resolution Structure of Monomorphic Aβ ₄₂ Amyloid Fibrils Colvin, Michael T.; Silvers, Robert; Ni, Qing Zhe Journal of the American Chemical Society, Vol. 138, Issue 30 https://doi.org/10.1021/jacs.6b05129	journal	July 2016
The α-to-β Conformational Transition of Alzheimer's Aβ-(1-42) Peptide in Aqueous Media is Reversible: A Step by Step Conformational Analysis Suggests the Location of β Conformation Seeding Tomaselli, Simona; Esposito, Veronica; Vangone, Paolo ChemBioChem, Vol. 7, Issue 2 https://doi.org/10.1002/cbic.200500223	journal	January 2006
A structural model for Alzheimer's -amyloid fibrils based on experimental constraints from solid state NMR Petkova, A. T.; Ishii, Y.; Balbach, J. J. Proceedings of the National Academy of Sciences, Vol. 99, Issue 26 https://doi.org/10.1073/pnas.262663499	journal	December 2002
Molecular basis for mid-region amyloid-β capture by leading Alzheimer's disease immunotherapies Crespi, Gabriela A. N.; Hermans, Stefan J.; Parker, Michael W. Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep09649	journal	April 2015
X-Ray Diffraction Studies on Amyloid Filaments Eanes, E. D.; Glenner, G. G. Journal of Histochemistry & Cytochemistry, Vol. 16, Issue 11 https://doi.org/10.1177/16.11.673	journal	November 1968
Modulation of β-amyloid by a single dose of GSK933776 in patients with mild Alzheimer's disease: a phase I study Leyhe, Thomas; Andreasen, Niels; Simeoni, Monica RWTH Aachen University https://doi.org/10.18154/rwth-conv-091140	text	January 2014
Monoclonal Antibody Against the Turn of the 42-Residue Amyloid β-Protein at Positions 22 and 23 Murakami, Kazuma; Horikoshi-Sakuraba, Yuko; Murata, Nakaba ACS Chemical Neuroscience, Vol. 1, Issue 11 https://doi.org/10.1021/cn100072e	journal	September 2010
Monoclonal antibody against the turn of the 42-residue amyloid β-protein at positions 22 and 23 Irie, Kazuhiro; Murakami, Kazuma; Masuda, Yuichi Rinsho Shinkeigaku, Vol. 51, Issue 11 https://doi.org/10.5692/clinicalneurol.51.890	journal	January 2011
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
A Therapeutic Antibody Targeting BACE1 Inhibits Amyloid- Production in Vivo Atwal, J. K.; Chen, Y.; Chiu, C. Science Translational Medicine, Vol. 3, Issue 84 https://doi.org/10.1126/scitranslmed.3002254	journal	May 2011
Conformation-specific antibodies to target amyloid β oligomers and their application to immunotherapy for Alzheimer’s disease Murakami, Kazuma Bioscience, Biotechnology, and Biochemistry, Vol. 78, Issue 8 https://doi.org/10.1080/09168451.2014.940275	journal	August 2014
Microglial p38α MAPK is critical for LPS-induced neuron degeneration, through a mechanism involving TNFα Xing, Bin; Bachstetter, Adam D.; Van Eldik, Linda J. Molecular Neurodegeneration, Vol. 6, Issue 1 https://doi.org/10.1186/1750-1326-6-84	journal	January 2011
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation Tillu, Vikas A.; Rae, James; Gao, Ya Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21035-4	journal	February 2021
The A4 Study: Stopping AD Before Symptoms Begin? Sperling, R. A.; Rentz, D. M.; Johnson, K. A. Science Translational Medicine, Vol. 6, Issue 228 https://doi.org/10.1126/scitranslmed.3007941	journal	March 2014
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes Benilova, Iryna; Karran, Eric; De Strooper, Bart Nature Neuroscience, Vol. 15, Issue 3 https://doi.org/10.1038/nn.3028	journal	January 2012
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
O4-11-06: a Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of Crenezumab in Patients with mild to Moderate Alzheimer'S Disease Cummings, Jeffrey; Cho, William; Ward, Michael Alzheimer's & Dementia, Vol. 10 https://doi.org/10.1016/j.jalz.2014.04.450	journal	July 2014
Aβ(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer's disease Xiao, Yiling; Ma, Buyong; McElheny, Dan Nature Structural & Molecular Biology, Vol. 22, Issue 6 https://doi.org/10.1038/nsmb.2991	journal	May 2015
Modulation of β-amyloid by a single dose of GSK933776 in patients with mild Alzheimer’s disease: a phase I study Leyhe, Thomas; Andreasen, Niels; Simeoni, Monica Alzheimer's Research & Therapy, Vol. 6, Issue 2 https://doi.org/10.1186/alzrt249	journal	January 2014
Deglycosylated Anti-Amyloid-beta Antibodies Eliminate Cognitive Deficits and Reduce Parenchymal Amyloid with Minimal Vascular Consequences in Aged Amyloid Precursor Protein Transgenic Mice Wilcock, D. M. Journal of Neuroscience, Vol. 26, Issue 20 https://doi.org/10.1523/JNEUROSCI.0695-06.2006	journal	May 2006
Amyloid-β–Anti-Amyloid-β Complex Structure Reveals an Extended Conformation in the Immunodominant B-Cell Epitope Miles, Luke A.; Wun, Kwok S.; Crespi, Gabriela A. N. Journal of Molecular Biology, Vol. 377, Issue 1 https://doi.org/10.1016/j.jmb.2007.12.036	journal	March 2008
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo Walsh, Dominic M.; Klyubin, Igor; Fadeeva, Julia V. Nature, Vol. 416, Issue 6880 https://doi.org/10.1038/416535a	journal	April 2002
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide Haass, Christian; Selkoe, Dennis J. Nature Reviews Molecular Cell Biology, Vol. 8, Issue 2 https://doi.org/10.1038/nrm2101	journal	February 2007
Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril Wälti, Marielle Aulikki; Ravotti, Francesco; Arai, Hiromi Proceedings of the National Academy of Sciences, Vol. 113, Issue 34 https://doi.org/10.1073/pnas.1600749113	journal	July 2016
Pure absorption gradient enhanced heteronuclear single quantum correlation spectroscopy with improved sensitivity Kay, Lewis; Keifer, Paul; Saarinen, Tim Journal of the American Chemical Society, Vol. 114, Issue 26 https://doi.org/10.1021/ja00052a088	journal	December 1992
Neuroinflammation in Alzheimer's disease Heneka, Michael T.; Carson, Monica J.; Khoury, Joseph El The Lancet Neurology, Vol. 14, Issue 4 https://doi.org/10.1016/s1474-4422(15)70016-5	journal	April 2015
PTEN regulates RPA1 and protects DNA replication forks Wang, Guangxi; Li, Yang; Wang, Pan Cell Research, Vol. 25, Issue 11 https://doi.org/10.1038/cr.2015.115	journal	September 2015
Unraveling the secrets of Alzheimer's β-amyloid fibrils Thompson, Lynmarie K. Proceedings of the National Academy of Sciences, Vol. 100, Issue 2 https://doi.org/10.1073/pnas.0337745100	journal	January 2003
Implications for Alzheimer’s disease of an atomic resolution structure of amyloid-β(1–42) fibrils Eisenberg, David S.; Sawaya, Michael R. Proceedings of the National Academy of Sciences, Vol. 113, Issue 34 https://doi.org/10.1073/pnas.1610806113	journal	August 2016
Antiparallel Triple-strand Architecture for Prefibrillar Aβ42 Oligomers Gu, Lei; Liu, Cong; Stroud, James C. Journal of Biological Chemistry, Vol. 289, Issue 39 https://doi.org/10.1074/jbc.m114.569004	journal	August 2014
An Effector-Reduced Anti- -Amyloid (A ) Antibody with Unique A Binding Properties Promotes Neuroprotection and Glial Engulfment of A Adolfsson, O.; Pihlgren, M.; Toni, N. Journal of Neuroscience, Vol. 32, Issue 28 https://doi.org/10.1523/jneurosci.4742-11.2012	journal	July 2012
Gantenerumab: A Novel Human Anti-Aβ Antibody Demonstrates Sustained Cerebral Amyloid-β Binding and Elicits Cell-Mediated Removal of Human Amyloid-β Bohrmann, Bernd; Baumann, Karlheinz; Benz, Jörg Journal of Alzheimer's Disease, Vol. 28, Issue 1 https://doi.org/10.3233/jad-2011-110977	journal	January 2012
New roles for Fc receptors in neurodegeneration-the impact on Immunotherapy for Alzheimer's Disease Fuller, James P.; Stavenhagen, Jeffrey B.; Teeling, Jessica L. Frontiers in Neuroscience, Vol. 8 https://doi.org/10.3389/fnins.2014.00235	journal	August 2014

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