Hu Junbin, Wu Yunkun, Li Jingzhi, Qian Xinguo, Fu Zhengqing, Sha Bingdong
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
BMC Struct Biol. 2008 Jan 22;8:3. doi: 10.1186/1472-6807-8-3.
The mechanism by which Hsp40 and other molecular chaperones recognize and interact with non-native polypeptides is a fundamental question. How Hsp40 co-operates with Hsp70 to facilitate protein folding is not well understood. To investigate the mechanisms, we determined the crystal structure of the putative peptide-binding fragment of Hdj1, a human member of the type II Hsp40 family.
The 2.7A structure reveals that Hdj1 forms a homodimer in the crystal by a crystallographic two-fold axis. The Hdj1 dimer has a U-shaped architecture and a large cleft is formed between the two elongated monomers. When compared with another Hsp40 Sis1 structure, the domain I of Hdj1 is rotated by 7.1 degree from the main body of the molecule, which makes the cleft between the two Hdj1 monomers smaller that that of Sis1.
This structural observation indicates that the domain I of Hsp40 may possess significant flexibility. This flexibility may be important for Hsp40 to regulate the size of the cleft. We propose an "anchoring and docking" model for Hsp40 to utilize the flexibility of domain I to interact with non-native polypeptides and transfer them to Hsp70.
热休克蛋白40（Hsp40）及其他分子伴侣识别并与非天然多肽相互作用的机制是一个基本问题。Hsp40如何与热休克蛋白70（Hsp70）协同促进蛋白质折叠尚不清楚。为了研究这些机制，我们测定了II型Hsp40家族人类成员Hdj1假定的肽结合片段的晶体结构。
2.7埃的结构显示，Hdj1在晶体中通过晶体学二重轴形成同二聚体。Hdj1二聚体具有U形结构，在两个细长的单体之间形成一个大裂缝。与另一个Hsp40 Sis1结构相比，Hdj1的结构域I相对于分子主体旋转了7.1度，这使得两个Hdj1单体之间的裂缝比Sis1的小。
这一结构观察表明，Hsp40的结构域I可能具有显著的灵活性。这种灵活性可能对Hsp40调节裂缝大小很重要。我们提出了一个“Hsp40利用结构域I的灵活性与非天然多肽相互作用并将它们转移给Hsp70的“锚定和对接”模型。
