Deciphering site 3 interactions of interleukin 12 and interleukin 23 with their cognate murine and human receptors.

ABSTRACT: Interleukin (IL)-12 and IL-23 belong to the IL-12 type family and are composite cytokines, consisting of the common β subunit p40 and the specific cytokine α subunit p35 and p19, respectively. IL-12 signals via the IL-12Rβ1·IL-12Rβ2 receptor complex, and IL-23 uses also IL-12Rβ1 but engages IL-23R as second receptor. Importantly, binding of IL-12 and IL-23 to IL-12Rβ1 is mediated by p40, and binding to IL-12Rβ2 and IL-23R is mediated by p35 and p19, respectively. Previously, we have identified a W157A substitution at site 3 of murine IL-23p19 that abrogates binding to murine IL-23R. Here, we demonstrate that the analogous Y185R site 3 substitution in murine and Y189R site 3 substitution in human IL-12p35 abolishes binding to IL-12Rβ2 in a cross-species manner. Although Trp¹⁵⁷ is

SUBMITTER: Esch A 

PROVIDER: S-EPMC7383385 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature