Unknown

Dataset Information

0

Third BIR domain of XIAP binds to both Cu(II) and Cu(I) in multiple sites and with diverse affinities characterized at atomic resolution.


ABSTRACT: The X-chromosome linked inhibitor of apoptosis, XIAP, is mainly known as the inhibitor of caspases by direct interaction with caspases with its baculoviral IAP repeat (BIR) domains. XIAP has three BIR domains and each BIR domain contains a zinc binding site, normally known as zinc finger motif. Recent studies showed that XIAP is involved in copper homeostasis in cells and the BIR domains bind copper ion. However, structural details of the second and third BIR domain, BIR2 and BIR3, in XIAP, with copper as well as the binding modes are not known. In the present work we characterize the structural properties of BIR3 in solution by high resolution NMR and other biophysical techniques. The interaction of BIR3 with copper both in vitro and in cell lysates was analyzed. Our results show that BIR3 is able to form stable complexes both with Cu(II) and Cu(I), whereas zinc binding site is not affected and zinc retains tightly bound in the zinc finger during these interactions. Surprisingly, BIR3 has multiple binding sites for Cu(II) and Cu(I) but with varied binding affinities. In addition, the solvent exposed Cys351 is readily oxidized by Cu(II) resulting an intermolecular disulfide bond either between two BIR3 molecules or a mixed disulfide bond with glutathione in cell lysates.

SUBMITTER: Chen SN 

PROVIDER: S-EPMC6520397 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Third BIR domain of XIAP binds to both Cu(II) and Cu(I) in multiple sites and with diverse affinities characterized at atomic resolution.

Chen Shen-Na SN   Fang Tian T   Kong Jing-Yang JY   Pan Bin-Bin BB   Su Xun-Cheng XC  

Scientific reports 20190515 1


The X-chromosome linked inhibitor of apoptosis, XIAP, is mainly known as the inhibitor of caspases by direct interaction with caspases with its baculoviral IAP repeat (BIR) domains. XIAP has three BIR domains and each BIR domain contains a zinc binding site, normally known as zinc finger motif. Recent studies showed that XIAP is involved in copper homeostasis in cells and the BIR domains bind copper ion. However, structural details of the second and third BIR domain, BIR2 and BIR3, in XIAP, with  ...[more]

Similar Datasets

| S-EPMC3760131 | biostudies-literature
| S-EPMC5709467 | biostudies-literature
| S-EPMC3084784 | biostudies-literature
| S-EPMC9692694 | biostudies-literature
| S-EPMC7179608 | biostudies-literature
| S-EPMC7401034 | biostudies-literature
| S-EPMC10390515 | biostudies-literature
| S-EPMC10485824 | biostudies-literature
| S-EPMC4572610 | biostudies-other
| S-EPMC11349198 | biostudies-literature