Department of Chemistry and Biochemistry, UCLA-DOE Institute of Genomics and Proteomics, Molecular Biology Institute, University of California, Los Angeles, Boyer Hall 611 Charles E. Young Dr. E., Los Angeles, California 90095-1570, USA.
Biochemistry. 2011 May 10;50(18):3807-15. doi: 10.1021/bi200141e. Epub 2011 Apr 15.
Liprins are a conserved family of scaffolding proteins important for the proper regulation and development of neuronal synapses. Humans have four liprin-αs and two liprin-βs which all contain long coiled-coil domains followed by three tandem SAM domains. Complex interactions between the coiled-coil and SAM domains are thought to create liprin scaffolds, but the structural and biochemical properties of these domains remain largely uncharacterized. In this study we find that the human liprin-β2 coiled-coil forms an extended dimer. Several protease-resistant subdomains within the liprin-β1 and liprin-β2 coiled-coils were also identified. A 2.0 Å crystal structure of the central, protease-resistant core of the liprin-β2 coiled-coil reveals a parallel helix orientation. These studies represent an initial step toward determining the overall architecture of liprin scaffolds and understanding the molecular basis for their synaptic functions.
脂质连接蛋白是一个保守的支架蛋白家族，对于神经元突触的正常调节和发育非常重要。人类有四个 liprin-α 和两个 liprin-β，它们都含有长的卷曲螺旋结构域，后面跟着三个串联的 SAM 结构域。卷曲螺旋和 SAM 结构域之间的复杂相互作用被认为可以形成脂质连接蛋白支架，但这些结构域的结构和生化特性在很大程度上仍未被描述。在这项研究中，我们发现人类的 liprin-β2 卷曲螺旋形成了一个扩展的二聚体。还鉴定了 liprin-β1 和 liprin-β2 卷曲螺旋中的几个蛋白酶抗性亚结构域。liprin-β2 卷曲螺旋中心蛋白酶抗性核心的 2.0 Å 晶体结构揭示了平行螺旋的取向。这些研究代表了确定脂质连接蛋白支架整体结构并理解其突触功能的分子基础的初始步骤。
