Structural relationship of kappa-type light chains with AL amyloidosis: multiple deletions found in a VkappaIV protein.
Two amyloidogenic Bence Jones proteins (Am37 VkappaIV and NIG1 VkappaI) and one non-amyloidogenic protein (NIG26 VkappaIII) were characterized. The protein Am37 had four deletions when compared with the translated germ-line gene sequence: two Ser residues following position 27 (27e, 27f) in CDR1 and two amino acids Pro-44, and Tyr-49 in FR2 were deleted. A strictly conserved salt-bridge-forming amino acid, Asp-82, was replaced by the hydrophobic residue Leu. In a comparative study of amyloidogenic and non-amyloidogenic proteins, five amino acids (Ser-10, Ala-13, Ser-65, Gln-90, and Ile-106) were found to be unique to NIG1 and several other amyloidogenic proteins. Additional substitutions also occur within these proteins. These substitutions might be significant in altering protein folding as well as in contributing to their aggregation as amyloid fibrils.
Alim
M A
MA
Department of Neurochemistry, Tokyo Institute of Psychiatry, Tokyo, Japan. alim@comp.metro-u.ac.jp
Yamaki
S
S
Hossain
M S
MS
Takeda
K
K
Kozima
M
M
Izumi
T
T
Takashi
I
I
Shinoda
T
T
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000596:Amino Acids / Q000032:analysis; D000686:Amyloidosis / Q000235:genetics* / Q000652:urine; D001536:Bence Jones Protein / Q000737:chemistry* / Q000235:genetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D018095:Germ-Line Mutation; D006801:Humans; D015151:Immunoblotting; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry* / Q000235:genetics / Q000652:urine; D008969:Molecular Sequence Data; D010865:Pilot Projects; D017421:Sequence Analysis; D017384:Sequence Deletion / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000596:Amino Acids; C402522:Bence Jones protein AM37; C402542:Bence Jones protein NIG1; C402562:Bence Jones protein NIG26; D007145:Immunoglobulin kappa-Chains; D001536:Bence Jones Protein