Page 20 - U. Protein structure and function

[U. Protein structure and function-15]

The Dynamic Structure of human Interleukin 33 in the apo

form

Se-Young Son¹˙#, Sang-Hyun Son¹, Young-Ha Ryu¹, Young Ho Jeon¹˙²˙*

¹Department of Structure analysis, Allercuris Co., Ltd., Sejong 30019, korea, ²College of Pharmacy, Korea University,

Sejong 30019, korea

Interleukin 33 (IL-33) has a critic role in the progression of allergic disease such as asthma and atopic dermatitis
(AD) through the type II immune responses. As a member of the IL-1 family, IL-33 consists of the 12 β-strands of

the β-trefoil and has four cysteine residues that form disulfide bonds. Currently, solution structure of IL-33 and

crystal structure of the complex of IL-33 and its receptor ST2 were reported. However, there is no report for the
crystal structure of IL-33 in its apo form. Once we discover this structure, it will be very useful for obtaining the
complex structure of IL-33 with potential small-molecule inhibitors. Here we report the structure of IL-33 apo form

with a mutation of cysteine to alanine at position of the reside 259. Compared to our structure and ST2 bound
form, there was a change in the residue located at the binding site. The major difference were Y122, Y163 on the

β strand 1. Y122 on the bound form is flipped outward, while in our structure it is gathered. Through structural
analysis, this part can be expected to be an active site that can inhibit the binding of IL-33 and ST2. Also Our results

provide information on drug design in the future.