부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jmb.2006.10.093 Byline: Leo C. James (1), Phil C. Jones (2), Airlie McCoy (3), Glenys A. Tennent (4), Mark B. Pepys (4), Kristoffer Famm (5), Greg Winter (1) Keywords: [beta]-edge; amyloid; aggregation; antibody; light-chain deposition disease Abbreviations: CDR, complementarity-determing region Abstract: Antibodies are the archetypal molecules of the Ig-fold superfamily. Their highly conserved [beta]-sheet architecture has evolved to avoid aggregation by protecting edge strands. However, the crystal structure of a human V[kappa] domain described here, reveals an exposed [beta]-edge strand which mediates assembly of a helical pentadecameric oligomer. This edge strand is highly conserved in V[kappa] domains but is both shortened and capped by the use of two sequential trans-proline residues in VI' domains. We suggest that the exposure of this [beta]-edge in V[kappa] domains may explain why light-chain deposition disease is mediated predominantly by [kappa] antibodies. Author Affiliation: (1) MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK (2) Domantis Limited, 315 Cambridge Science Park, Cambridge, CB4 0WG, UK (3) Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK (4) Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, London NW3 2PF, UK (5) MRC Centre for Protein Engineering, Hills Road, Cambridge, CB2 2QH, UK Article History: Received 12 September 2006; Revised 25 October 2006; Accepted 26 October 2006 Article Note: (miscellaneous) Edited by I. Wilson