Analysis of internal motions of interleukin-13 variant associated with severe bronchial asthma using N NMR relaxation measurements

Yoshida, Yuichiro*; Okuri, Takatoshi*; Takeda, Chika*; Kuroki, Ryota; Izuhara, Kenji*; Imoto, Taiji*; Ueda, Tadashi*

The single nucleotide polymorphism interleukin-13 (IL-13) R110Q is associated with severe bronchial asthma because its lower affinity leads to the augmentation of local IL-13 concentration, resulting in an increase in the signal transduction via IL-13R. Since the mutation site does not directly bind to IL-13 R2, we carried out NMR relaxation analyses of the wild-type IL-13 and IL-13 R110Q in order to examine whether the R110Q mutation affects the internal motions in IL-13 molecules. The results showed that the internal motion in the micro- to millisecond time scale on helix D, which is suggested to be important for the interaction between IL-13 and IL-13R2, is increased in IL-13-R110Q compared with that in the wild-type IL-13. It therefore appears that the difference in the internal motions on helix D between the wild-type IL-13 and IL-13-R110Q may be involved in their affinity differences with IL-13R2.