Kim S J, Jeong D G, Chi S W, Lee J S, Ryu S E
Center for Cellular Switch Protein Structure, Korea Research Institute of Bioscience and Biotechnology, P. O. Box 115, Yusong, Taejon 305-600, South Korea.
Nat Struct Biol. 2001 May;8(5):459-66. doi: 10.1038/87639.
Heat shock protein 33 (Hsp33) inhibits aggregation of partially denatured proteins during oxidative stress. The chaperone activity of Hsp33 is unique among heat shock proteins because the activity is reversibly regulated by cellular redox status. We report here the crystal structure of the N-terminal region of Hsp33 fragments with constitutive chaperone activity. The structure reveals that the N-terminal portion of Hsp33 forms a tightly associated dimer formed by a domain crossover. A concave groove on the dimeric surface contains an elongated hydrophobic patch that could potentially bind denatured protein substrates. The termini of the subunits are located near the hydrophobic patch, indicating that the cleaved C-terminal domain may shield the hydrophobic patch in an inactive state. Two of the four conserved zinc-coordinating cysteines are in the end of the N-terminal domain, and the other two are in the cleaved C-terminal domain. The structural information and subsequent biochemical characterizations suggest that the redox switch of Hsp33 occurs by a reversible dissociation of the C-terminal regulatory domain through oxidation of zinc-coordinating cysteines and zinc release.
热休克蛋白33（Hsp33）在氧化应激期间抑制部分变性蛋白质的聚集。Hsp33的伴侣活性在热休克蛋白中是独特的，因为该活性受细胞氧化还原状态的可逆调节。我们在此报告具有组成型伴侣活性的Hsp33片段N端区域的晶体结构。该结构表明，Hsp33的N端部分形成由结构域交叉形成的紧密结合二聚体。二聚体表面的凹槽包含一个细长的疏水补丁，可能与变性蛋白质底物结合。亚基的末端位于疏水补丁附近，表明切割后的C端结构域可能在无活性状态下屏蔽疏水补丁。四个保守的锌配位半胱氨酸中的两个位于N端结构域的末端，另外两个位于切割后的C端结构域中。结构信息及后续生化特性表明，Hsp33的氧化还原开关是通过锌配位半胱氨酸的氧化和锌释放导致C端调节结构域的可逆解离而发生的。
