Analysis of internal motions of interleukin-13 variant associated with severe bronchial asthma using (15)N NMR relaxation measurements.
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-13Ralpha2, 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-13Ralpha2, 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-13Ralpha2.
Yoshida
Yuichiro
Y
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Ohkuri
Takatoshi
T
Takeda
Chika
C
Kuroki
Ryota
R
Izuhara
Kenji
K
Imoto
Taiji
T
Ueda
Tadashi
T
D001249:Asthma / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000737:chemistry* / Q000235:genetics; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000737:chemistry; D008958:Models, Molecular; D009038:Motion; D019906:Nuclear Magnetic Resonance, Biomolecular; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation
D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit