Structure of a human IgA1 Fab fragment at 1.55 Å resolution: potential effect of the constant domains on antigen-affinity modulation.

Agustin Correa (1) , Felipe Trajtenberg (2) , Gonzalo Obal (1) , Otto Pritsch (1, 3) , Guillermo Dighiero (1) , Pablo Oppezzo (1) , Alejandro Buschiazzo (2, 4)

1 Institut Pasteur de Montevideo
2 Protein Crystallography / Cristalografía de Proteínas [Montevideo]
3 Department of Immunobiology
4 Biochimie Structurale

Despite being the most abundant class of immunoglobulins in humans and playing central roles in the adaptive immune response, high-resolution structural data are still lacking for the antigen-binding region of human isotype A antibodies (IgAs). The crystal structures of a human Fab fragment of IgA1 in three different crystal forms are now reported. The three-dimensional organization is similar to those of other Fab classes, but FabA1 seems to be more rigid, being constrained by a hydrophobic core in the interface between the variable and constant domains of the heavy chain (VH-CH1) as well as by a disulfide bridge that connects the light and heavy chains, influencing the relative heavy/light-chain orientation. The crystal structure of the same antibody but with a G-isotype CH1 which is reported to display different antigen affinity has also been solved. The differential structural features reveal plausible mechanisms for constant/variable-domain long-distance effects whereby antibody class switching could alter antigen affinity.

Domains: Life Sciences [q-bio]

Agustin Correa, Felipe Trajtenberg, Gonzalo Obal, Otto Pritsch, Guillermo Dighiero, et al.. Structure of a human IgA1 Fab fragment at 1.55 Å resolution: potential effect of the constant domains on antigen-affinity modulation.. Acta crystallographica Section D : Structural biology [1993-..], 2013, 69 (Pt 3), pp.388-97. ⟨10.1107/S0907444912048664⟩. ⟨pasteur-00847149⟩