Conformational selection in amyloid-based immunotherapy: Survey of crystal structures of antibody-amyloid complexes

Buyong Ma*, Jun Zhao, Ruth Nussinov

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background The dominant feature in neurodegenerative diseases is protein aggregations that lead to neuronal loss. Immunotherapies using antibodies or antibody fragments to target the aggregations are a highly perused approach. The molecular mechanisms underlying the amyloid-based immunotherapy are complex. Deciphering the properties of amyloidogenic proteins responsible for these diseases is essential to obtain insights into antibody recognition of the amyloid antigens. Scope of review We systematically explore all available crystal structures of antibody-amyloid complexes related to neurodegenerative diseases, including antibodies that recognize the Aβ peptide, tau protein, prion protein, alpha-synuclein, huntingtin protein (mHTT), and polyglutamine. Major conclusions We found that antibodies mostly use the conformational selection mechanism to recognize the highly flexible amyloid antigens. In particular, solanezumab bound to Aβ12–28 tripeptide motif conformation (F19F20A21), which is shared with the Aβ42 fibril. This motif, which is trapped by the antibody, may provide the missing link in amyloid formation. Water molecules often bridge between the antibody and amyloid, contributing to the recognition. General significance This paper provides the structural basis for antibody recognition of amyloidogenic proteins. The analysis and discussion of known structures are expected to help in the design and optimization of antibodies in neurodegenerative diseases. This article is part of a Special Issue entitled “System Genetics” Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.

Original languageEnglish
Pages (from-to)2672-2681
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Issue number11
StatePublished - 1 Nov 2016


  • Alzheimer's disease
  • Amyloid
  • Antibody
  • Antigen
  • Biological drug
  • Neurodegenerative diseases
  • Prion


Dive into the research topics of 'Conformational selection in amyloid-based immunotherapy: Survey of crystal structures of antibody-amyloid complexes'. Together they form a unique fingerprint.

Cite this