Membrane Transport Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137 Blindern, 0318, Oslo, Norway.
Institute for Experimental Medical Research (IEMR), Oslo University Hospital, Ullevål PB 4956 Nydalen, NO-0424, Oslo, Norway.
Commun Biol. 2020 Mar 13;3(1):123. doi: 10.1038/s42003-020-0851-2.
Sjögren syndrome/scleroderma autoantigen 1 (SSSCA1) was first described as an auto-antigen over-expressed in Sjögren's syndrome and in scleroderma patients. SSSCA1 has been linked to mitosis and centromere association and as a potential marker candidate in diverse solid cancers. Here we characterize SSSCA1 for the first time, to our knowledge, at the molecular, structural and subcellular level. We have determined the crystal structure of a zinc finger fold, a zinc ribbon domain type 2 (ZNRD2), at 2.3 Å resolution. We show that the C-terminal domain serves a dual function as it both behaves as the interaction site to Tankyrase 1 (TNKS1) and as a nuclear export signal. We identify TNKS1 as a direct binding partner of SSSCA1, map the binding site to TNKS1 ankyrin repeat cluster 2 (ARC2) and thus define a new binding sequence. We experimentally verify and map a new nuclear export signal sequence in SSSCA1.
干燥综合征/硬皮病自身抗原 1（SSSCA1）最初被描述为在干燥综合征和硬皮病患者中过度表达的自身抗原。SSSCA1 与有丝分裂和着丝粒关联有关，并且是多种实体癌中的潜在候选标志物。在这里，我们首次在分子、结构和亚细胞水平上对 SSSCA1 进行了表征。我们以 2.3Å 的分辨率确定了锌指折叠、锌 ribbon 结构域类型 2（ZNRD2）的晶体结构。我们表明，C 端结构域具有双重功能，既是 Tankyrase 1（TNKS1）的相互作用位点，也是核输出信号。我们鉴定 TNKS1 为 SSSCA1 的直接结合伴侣，将结合位点映射到 TNKS1 的 ankyrin 重复簇 2（ARC2），从而定义了一个新的结合序列。我们通过实验验证并在 SSSCA1 中映射了一个新的核输出信号序列。
