Glycosylation of immunoglobulin light chains associated with amyloidosis.
AL amyloidosis is a fatal disease caused by deposition of immunoglobulin light chains in a fibrillarforin (AL) in various organs. By searching the Kabat database of immunoglobulin sequences using the KabatMan software, we have shown that there is a preponderance of the consensus glycosylation sequon (AsnXxxSer/Thr) in the framework regions of amyloid light chains. We have characterised by computer graphics simulations, NMR spectroscopy and carbohydrate biochemistry the structure and conformation of the oligosaccharide from amyloid protein AL MS (lamba1) and from the amyloid associated Bence Jones protein of patient MH (kappa1). These proteins have glycosylation in the hypervariable complementarity-determining region versus framework region, respectively. Both contained a 2-6 sialylated core fucosylated biantennary chain mostly with bisecting GIcNAc. Together our results suggest that light chain glycosylation may be one of several modifications which may render the protein more prone to amyloid formation.
Omtvedt
L A
LA
Biotechnology Centre of Oslo, University of Oslo, Norway.
Bailey
D
D
Renouf
D V
DV
Davies
M J
MJ
Paramonov
N A
NA
Haavik
S
S
Husby
G
G
Sletten
K
K
Hounsell
E F
EF
D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
D007147:Immunoglobulin Light Chains