Probing transient non-native states in amyloid beta fiber elongation by NMR

Jeffrey R. Brender; Anirban Ghosh; Samuel A. Kotler; Janarthanan Krishnamoorthy; Swapna Bera; Vanessa Morris; Timir Baran Sil; Kanchan Garai; Bernd Reif; Anirban Bhunia; Ayyalusamy Ramamoorthy

doi:10.1039/C9CC01067J

Probing transient non-native states in amyloid beta fiber elongation by NMR†

Jeffrey R. Brender,

‡^ab Anirban Ghosh,‡^c Samuel A. Kotler,‡^b Janarthanan Krishnamoorthy,^abd Swapna Bera,^c Vanessa Morris,

^e Timir Baran Sil,^f Kanchan Garai,^f Bernd Reif,

^e Anirban Bhunia

*^abc and Ayyalusamy Ramamoorthy

*^abg

Author affiliations

* Corresponding authors

^a Biophysics, University of Michigan, Ann Arbor, MI 48109-1055, USA
E-mail: ramamoor@umich.edu

^b Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA

^c Department of Biophysics, Bose Institute, Kolkata 700054, India
E-mail: bhunia@jcbose.ac.in

^d VClinbio Labs Pvt Ltd, Sri Ramchandra Medical Center, Chennai 600116, India

^e Department of Chemistry, Technische Universität München, Germany

^f TIFR Centre for Interdisciplinary Sciences, Hyderabad 500107, India

^g Institute of Advanced Studies, Technische Universität München, Germany

Abstract

Using NMR to probe transient binding of Aβ_1–40 monomers to fibers, we find partially bound conformations with the highest degree of interaction near F19–K28 and a lesser degree of interaction near the C-terminus (L34–G37). This represents a shift away from the KLVFFA recognition sequence (residues 16–21) currently used for inhibitor design.

Chemical Communications

Probing transient non-native states in amyloid beta fiber elongation by NMR†

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Probing transient non-native states in amyloid beta fiber elongation by NMR

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