人类 38 阴性激酶 1 (TNK1) 与癌症进展有关。 TNK1 泛素相关 (UBA) 结构域结合多聚泛素，在 TNK1 活性和稳定性中发挥调节作用。对于这个不寻常的 UBA 结构域，目前还没有通过实验确定的分子结构。我们将 UBA 结构域与易位 ETS 白血病蛋白不育 α 基序 (TELSAM) 结晶伴侣的 1TEL 变体融合，并获得衍射高达 1.53 Å 的晶体。 GG 和 GSGG 连接子使 UBA 能够可重复地找到针对其宿主 1TEL 聚合物的高效结合模式，并在低至 0.2 mg/mL 的蛋白质浓度下结晶。我们的研究支持 1TEL 融合结晶机制，并表明 1TEL 融合晶体比传统蛋白质晶体需要更少的晶体接触。建模和实验验证表明 UBA 结构域可能对多聚泛素链的长度和连接具有选择性。版权所有 © 2023 作者。由爱思唯尔有限公司出版。保留所有权利。

Human thirty-eight-negative kinase-1 (TNK1) is implicated in cancer progression. The TNK1 ubiquitin-associated (UBA) domain binds polyubiquitin and plays a regulatory role in TNK1 activity and stability. No experimentally determined molecular structure of this unusual UBA domain is available. We fused the UBA domain to the 1TEL variant of the translocation ETS leukemia protein sterile alpha motif (TELSAM) crystallization chaperone and obtained crystals diffracting as far as 1.53 Å. GG and GSGG linkers allowed the UBA to reproducibly find a productive binding mode against its host 1TEL polymer and crystallize at protein concentrations as low as 0.2 mg/mL. Our studies support a mechanism of 1TEL fusion crystallization and show that 1TEL fusion crystals require fewer crystal contacts than traditional protein crystals. Modeling and experimental validation suggest the UBA domain may be selective for both the length and linkages of polyubiquitin chains.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.