Influence of the mu-chain C-terminal sequence on polymerization of immunoglobulin M.
Immunoglobulin (IgM) is found in various states of covalent polymerization (microL)n, where n is typically 8, 10, or 12. The usual form of IgM of bony fish is tetrameric (8 microL units) as compared to the pentameric form (10 microL units) observed in cartilaginous fish and mammals. Two hypotheses were tested in this study. First, that the length of the mu-chain C terminus following Cys575 determines whether an IgM polymerizes as a tetramer or as a pentamer. This was tested by examining the covalent polymerization state of mouse IgM mutated to contain a series of mu-chain C-termini from bony and cartilaginous fish. The results proved this hypothesis wrong: mouse IgM bearing the C-terminal sequence of shark, salmon and cod mu-chain behaved identically to native mouse IgM, forming predominantly (microL)10 and (microL)12 forms. The second hypothesis was that an additional Cys residue near the C terminus of the mu-chain is responsible for the multiple covalent structures seen in IgM of the channel catfish. The addition of a catfish C terminus to the mouse mu-chain resulted, as predicted, in the production of a series of covalently bonded forms, with the major species being (microL)4. When a Ser-Cys unit was removed from the catfish C terminus added to the mouse mu-chain, this resulted in production of IgM indistinguishable in structure from that of wild-type mouse IgM.
Getahun
A
A
Immunology Programme, Department of Cell and Molecular Biology, BMC, Uppsala University, Uppsala, Sweden.
Lundqvist
M
M
Middleton
D
D
Warr
G
G
Pilström
L
L
D000818:Animals; D002397:Catfishes / Q000276:immunology; D018929:Cell Culture Techniques; D002460:Cell Line; D046508:Culture Techniques; D004591:Electrophoresis, Polyacrylamide Gel; D005399:Fishes / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000737:chemistry*; D007148:Immunoglobulin mu-Chains / Q000737:chemistry* / Q000235:genetics; D046911:Macromolecular Substances; D051379:Mice; D016133:Polymerase Chain Reaction; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship
D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D046911:Macromolecular Substances