Wu Yunkun, Li Jingzhi, Jin Zhongmin, Fu Zhengqing, Sha Bingdong
Department of Cell Biology, Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
J Mol Biol. 2005 Mar 4;346(4):1005-11. doi: 10.1016/j.jmb.2004.12.040. Epub 2005 Jan 16.
The molecular chaperone Hsp40 functions as a dimer. The dimer formation is critical for Hsp40 molecular chaperone activity to facilitate Hsp70 to refold non-native polypeptides. We have determined the crystal structure of the C-terminal fragment of yeast Hsp40 Ydj1 that is responsible for Ydj1 dimerization by MAD method. The C-terminal fragment of Ydj1 comprises of the domain III of Ydj1 and the Ydj1 C-terminal dimerization motif. The crystal structure indicates that the dimerization motif of type I Hsp40 Ydj1 differs significantly from that of yeast type II Hsp40. The C terminus of type I Hsp40 Ydj1 from one monomer forms beta-strands with the domain III from the other monomer in the homo-dimer. The L372 from Ydj1 C terminus inserts its side-chain into a hydrophobic pocket on domain III. The modeled full-length Ydj1 dimer structure reveals that a large cleft is formed between the two monomers. The domain IIs of Ydj1 monomers that contain the zinc-finger motifs points directly against each other.
分子伴侣Hsp40以二聚体形式发挥作用。二聚体的形成对于Hsp40分子伴侣活性至关重要，有助于Hsp70重新折叠非天然多肽。我们通过分子置换法确定了酵母Hsp40 Ydj1负责Ydj1二聚化的C端片段的晶体结构。Ydj1的C端片段由Ydj1的结构域III和Ydj1 C端二聚化基序组成。晶体结构表明，I型Hsp40 Ydj1的二聚化基序与酵母II型Hsp40的二聚化基序有显著差异。在同型二聚体中，一个单体的I型Hsp40 Ydj1的C末端与另一个单体的结构域III形成β链。Ydj1 C末端的L372将其侧链插入结构域III上的一个疏水口袋中。模拟的全长Ydj1二聚体结构显示，两个单体之间形成了一个大裂缝。含有锌指基序的Ydj1单体的结构域II直接相对。
