Structural requirements for polymeric immunoglobulin assembly and association with J chain.
Both IgM and IgA exist as polymeric immunoglobulins. IgM is assembled into pentamers with J chain and hexamers lacking J chain. In contrast, polymeric IgA exists mostly as dimers with J chain. Both IgM and IgA possess an 18-amino acid extension of the C terminus (the tail-piece (tp)) that participates in polymerization through a penultimate cysteine residue. The IgM (mutp) and IgA (alphatp) tail-pieces differ at seven amino acid positions. However, the tail-pieces by themselves do not determine the extent of polymerization. We now show that the restriction of polymerization to dimers requires both C(alpha)3 and alphatp and that more efficient dimer assembly occurs when C(alpha)2 is also present; the dimers contain J chain. Formation of pentamers containing J chain requires C(mu)3, C(mu)4, and the mutp. IgM-alphatp is present mainly as hexamers lacking J chain, and mumugammamu-utp forms tetramers and hexamers lacking J chain, whereas IgA-mutp is present as high order polymers containing J chain. In addition, there is heterogeneous processing of the N-linked carbohydrate on IgA-mutp, with some remaining in the high mannose state. These data suggest that in addition to the tail-piece, structural motifs in the constant region domains are critical for polymer assembly and J chain incorporation.
Yoo
E M
EM
Department of Microbiology, Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
Coloma
M J
MJ
Trinh
K R
KR
Nguyen
T Q
TQ
Vuong
L U
LU
Morrison
S L
SL
Chintalacharuvu
K R
KR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001704:Biopolymers; D017931:DNA Primers; D019281:Dimerization; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry / Q000378:metabolism*; D007075:Immunoglobulin M / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D001704:Biopolymers; D017931:DNA Primers; D007070:Immunoglobulin A; D007075:Immunoglobulin M