Pletnev Sergei, Magracheva Eugenia, Kozlov Serguei, Tobin Gregory, Kotenko Sergei V, Wlodawer Alexander, Zdanov Alexander
Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Maryland 21702-1201, USA.
Biochemistry. 2003 Nov 4;42(43):12617-24. doi: 10.1021/bi0354583.
The soluble extracellular domains of human interleukin-20 (IL-20) receptors I and II (sIL-20R1 and sIL20R2), along with their ligands IL-19 and IL-20, were expressed in Drosophila S2 cells and purified to homogeneity. Formation of the receptor/receptor and ligand/receptor complexes was studied by size exclusion chromatography. Both ligands and soluble receptors were found to be monomeric in solution; homo- or heterodimers are not formed even at elevated concentrations. Under native conditions, both IL-19 and IL-20 form stable ternary 1:1:1 complexes with the sIL-20R1 and sIL20R2 receptors, as well as high-affinity binary complexes with sIL-20R2. Unexpectedly, sIL-20R1 does not bind on its own to either IL-19 or IL-20. Thus, one of the possible consecutive mechanisms of formation of the signaling ternary complex may involve two steps: first, the ligand binds to receptor II, creating a high-affinity binding site for the receptor I, and only then does receptor I complete the complex.
人白细胞介素20（IL-20）受体I和II（sIL-20R1和sIL20R2）的可溶性细胞外结构域，连同其配体IL-19和IL-20，在果蝇S2细胞中表达并纯化至同质。通过尺寸排阻色谱法研究受体/受体和配体/受体复合物的形成。发现配体和可溶性受体在溶液中均为单体；即使在高浓度下也不会形成同二聚体或异二聚体。在天然条件下，IL-19和IL-20均与sIL-20R1和sIL20R2受体形成稳定的三元1:1:1复合物，以及与sIL-20R2形成高亲和力的二元复合物。出乎意料的是，sIL-20R1自身不与IL-19或IL-20结合。因此，信号三元复合物形成的可能连续机制之一可能涉及两个步骤：首先，配体与受体II结合，为受体I创造一个高亲和力结合位点，然后受体I才完成复合物的形成。
