Nature Communications (Apr 2018)
Conformational dynamics in crystals reveal the molecular bases for D76N beta-2 microglobulin aggregation propensity
- Tanguy Le Marchand,
- Matteo de Rosa,
- Nicola Salvi,
- Benedetta Maria Sala,
- Loren B. Andreas,
- Emeline Barbet-Massin,
- Pietro Sormanni,
- Alberto Barbiroli,
- Riccardo Porcari,
- Cristiano Sousa Mota,
- Daniele de Sanctis,
- Martino Bolognesi,
- Lyndon Emsley,
- Vittorio Bellotti,
- Martin Blackledge,
- Carlo Camilloni,
- Guido Pintacuda,
- Stefano Ricagno
Affiliations
- Tanguy Le Marchand
- Centre de RMN à Très Hauts Champs, Institut des Sciences Analytiques (UMR 5280 CNRS/UCB Lyon 1/ENS Lyon), Université de Lyon
- Matteo de Rosa
- Dipartimento di Bioscienze, Università degli Studi di Milano
- Nicola Salvi
- Institut de Biologie Structurale, CNRS, CEA, UGA
- Benedetta Maria Sala
- Dipartimento di Bioscienze, Università degli Studi di Milano
- Loren B. Andreas
- Centre de RMN à Très Hauts Champs, Institut des Sciences Analytiques (UMR 5280 CNRS/UCB Lyon 1/ENS Lyon), Université de Lyon
- Emeline Barbet-Massin
- Centre de RMN à Très Hauts Champs, Institut des Sciences Analytiques (UMR 5280 CNRS/UCB Lyon 1/ENS Lyon), Université de Lyon
- Pietro Sormanni
- Department of Chemistry, University of Cambridge
- Alberto Barbiroli
- Dipartimento di Scienze per gli Alimenti, la Nutrizione e l’Ambiente, Università degli Studi di Milano
- Riccardo Porcari
- Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London
- Cristiano Sousa Mota
- ESRF - The European Synchrotron
- Daniele de Sanctis
- ESRF - The European Synchrotron
- Martino Bolognesi
- Dipartimento di Bioscienze, Università degli Studi di Milano
- Lyndon Emsley
- Centre de RMN à Très Hauts Champs, Institut des Sciences Analytiques (UMR 5280 CNRS/UCB Lyon 1/ENS Lyon), Université de Lyon
- Vittorio Bellotti
- Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London
- Martin Blackledge
- Institut de Biologie Structurale, CNRS, CEA, UGA
- Carlo Camilloni
- Dipartimento di Bioscienze, Università degli Studi di Milano
- Guido Pintacuda
- Centre de RMN à Très Hauts Champs, Institut des Sciences Analytiques (UMR 5280 CNRS/UCB Lyon 1/ENS Lyon), Université de Lyon
- Stefano Ricagno
- Dipartimento di Bioscienze, Università degli Studi di Milano
- DOI
- https://doi.org/10.1038/s41467-018-04078-y
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 11
Abstract
The aggregation prone D76N beta-2 microglobulin mutant causes systemic amyloidosis. Here the authors combine crystallography, solid-state NMR, and computational studies and show that the D76N mutation increases protein dynamics and destabilizes the outer strands, which leads to an exposure of amyloidogenic parts explaining its aggregation propensity.
