Structural and functional studies of Igalphabeta and its assembly with the B cell antigen receptor.
The B cell antigen receptor (BCR) plays an essential role in all phases of B cell development. Here we show that the extracellular domains of murine and human Igbeta form an I-set immunoglobulin-like structure with an interchain disulfide between cysteines on their G strands. Structural and sequence analysis suggests that Igalpha displays a similar fold as Igbeta. An Igalphabeta heterodimer model was generated based on the unique disulfide-bonded Igbeta dimer. Solution binding studies showed that the extracellular domains of Igalphabeta preferentially recognize the constant region of BCR with mu chain specificity, suggesting a role for Igalphabeta to enhance BCRmu chain signaling. Cluster mutations on Igalpha, Igbeta, and a membrane-bound form of immunoglobulin (mIgM) based on the structural model identified distinct areas of potential contacts involving charged residues on both subunits of the coreceptor and the Cmu4 domain of mIgM. These studies provide the first structural model for understanding BCR function.
Radaev
Sergei
S
Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA.
Zou
Zhongcheng
Z
Tolar
Pavel
P
Nguyen
Khanh
K
Nguyen
AnhThao
A
Krueger
Peter D
PD
Stutzman
Nicole
N
Pierce
Susan
S
Sun
Peter D
PD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051925:CD79 Antigens / Q000737:chemistry* / Q000378:metabolism; D003461:Crystallography; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D019281:Dimerization; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D013045:Species Specificity; D020349:Surface Plasmon Resonance
D051925:CD79 Antigens; C497882:Cd79a protein, mouse; D017931:DNA Primers; D011947:Receptors, Antigen, B-Cell