Influence of the germline sequence on the thermodynamic stability and fibrillogenicity of human lambda 6 light chains
Por:
Yauner, LD, Ortiz E., Sánchez R., Sánchez-López R., Güereca L., Murphy C.L., Allen A., Wall J.S., Fernández-Velasco D.A., Solomon A., Becerril B.
Publicada:
1 ago 2008
Resumen:
Light chain-associated amyloidosis is a fatal disease characterized by the aggregation and pathologic deposition of monoclonal light chain-related fragments as amyloid fibrils in organs or tissues throughout the body. Notably, it has been observed that proteins encoded by the lambda variable light chain (V(L)) gene segment 6a are invariably associated with amyloid deposition; however, the contribution of the gene to this phenomenon has not been established. In this regard, we have determined the thermodynamic stability and kinetics of in vitro fibrillogenesis of a recombinant (r) V(L) protein, designated 6aJL2, which contains the predicted sequences encoded by the 6a and JL2 germline genes. Additionally, studied a 6a mutant (6aJL2-Arg25Gly), that is present in similar to 25% of all amyloid-associated lambda 6 light chains. Remarkably, the wild-type 6aJL2 protein was more stable than were all known amyloidogenic kappa and lambda light chains for which stability parameters are available;
Filiaciones:
Yauner, LD:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
Ortiz E.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
Sánchez R.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
Sánchez-López R.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
Güereca L.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
Murphy C.L.:
Human Immunology and Cancer Program, University of Tennessee Graduate School of Medicine, Knoxville, TN, United States
Allen A.:
Human Immunology and Cancer Program, University of Tennessee Graduate School of Medicine, Knoxville, TN, United States
Wall J.S.:
Human Immunology and Cancer Program, University of Tennessee Graduate School of Medicine, Knoxville, TN, United States
Fernández-Velasco D.A.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Bioquim, Lab Fisicoquim Prot, Cuernavaca 62210, Morelos, Mexico
Solomon A.:
Human Immunology and Cancer Program, University of Tennessee Graduate School of Medicine, Knoxville, TN, United States
Becerril B.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
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