National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing, 100101, China.
Structure Biology Laboratory, Tsinghua University, Beijing, 100084, China.
Protein Cell. 2010 Apr;1(4):406-416. doi: 10.1007/s13238-010-0049-3. Epub 2010 May 8.
Nascent polypeptide associated complex (NAC) and its two isolated subunits, αNAC and βNAC, play important roles in nascent peptide targeting. We determined a 1.9 Å resolution crystal structure of the interaction core of NAC heterodimer and a 2.4 Å resolution crystal structure of αNAC NAC domain homodimer. These structures provide detailed information of NAC heterodimerization and αNAC homodimerization. We found that the NAC domains of αNAC and βNAC share very similar folding despite of their relative low identity of amino acid sequences. Furthermore, different electric charge distributions of the two subunits at the NAC interface provide an explanation to the observation that the heterodimer of NAC complex is more stable than the single subunit homodimer. In addition, we successfully built a βNAC NAC domain homodimer model based on homologous modeling, suggesting that NAC domain dimerization is a general property of the NAC family. These 3D structures allow further studies on structure-function relationship of NAC.
新生多肽相关复合物（NAC）及其两个分离的亚基，αNAC 和 βNAC，在新生肽靶向中发挥重要作用。我们确定了 NAC 异二聚体相互作用核心的 1.9Å分辨率晶体结构和αNAC NAC 结构域同二聚体的 2.4Å分辨率晶体结构。这些结构提供了 NAC 异二聚化和αNAC 同二聚化的详细信息。我们发现，尽管 αNAC 和 βNAC 的 NAC 结构域的氨基酸序列相对较低，但它们具有非常相似的折叠。此外，在 NAC 界面处两个亚基的不同电荷分布为观察到的 NAC 复合物的异二聚体比单个亚基同二聚体更稳定提供了一个解释。此外，我们还成功地基于同源建模构建了一个βNAC NAC 结构域同二聚体模型，表明 NAC 结构域二聚化是 NAC 家族的一个普遍特性。这些 3D 结构允许对 NAC 的结构-功能关系进行进一步研究。
