tailieunhanh - Báo cáo khoa học: D-strand perturbation and amyloid propensity in beta-2 microglobulin

Proteins hosting mainb-sheets adopt specific strategies to avoid intermolec-ular interactions leading to aggregation and amyloid deposition. Human beta-2 microglobulin (b2m) displays a typical immunoglobulin fold and is known to be amyloidogenicin vivo. | BFEBS Journal D-strand perturbation and amyloid propensity in beta-2 microglobulin Stavros Azinas1 2 Matteo Colombo1 Alberto Barbiroli3 Carlo Santambrogio4 Sofia Giorgetti5 6 Sara Raimondi5 6 Francesco Bonomi3 Rita Grandori4 Vittorio Bellotti5 6 Stefano Ricagno1 and Martino Bolognesi1 1 Dipartimento di Scienze Biomolecolari e Biotecnologie and CIMAINA University degli Studi di Milano Milan Italy 2 Department of BiochemicalSciences University of Surrey Guildford UK 3 Dipartimento di Scienze Molecolari Agroalimentari Universita degli Studi di Milano Milan Italy 4 Dipartimento di Biotecnologie e Bioscienze Universita di Milano-Bicocca Milan Italy 5 Dipartimento di Biochimica University di Pavia Pavia Italy 6 Laboratori di Biotecnologie IRCCS Fondazione Policlinico San Matteo Pavia Italy Keywords amyloidosis beta-2 microglobulin beta-buldge dialysis related amyloidosis MHC I proline Correspondence M. Bolognesi Dipartimento di Scienze Biomolecolari e Biotecnologie and CIMAINA Universita degli Studi di Milano Via Celoria 26 20133 Milano Italy Fax 00390250314895 Tel 00390250314893 E-mail Received 21 March 2011 revised 29 April 2011 accepted 4 May 2011 doi Proteins hosting main b-sheets adopt specific strategies to avoid intermolec-ular interactions leading to aggregation and amyloid deposition. Human beta-2 microglobulin b2m displays a typical immunoglobulin fold and is known to be amyloidogenic in vivo. Upon severe kidney deficiency b2m accumulates in the bloodstream triggering over the years pathological deposition of large amyloid aggregates in joints and bones. A b-bulge observed on the edge D b-strand of some b2m crystal structures has been suggested to be crucial in protecting the protein from amyloid aggregation. Conversely a straight D-strand observed in different crystal structures of monomeric b2m could promote amyloid aggregation. More recently the different conformations observed for the b2m D-strand