2011年新学期伊始，国际重要学术期刊 Proceedings of the National Academy of Sciences 在线发表了南开大学生命科学学院胡俊杰和刘新奇课题组合作的最新研究成果，该成果揭示了嵌膜GTP酶Atlastin介导内质网膜融合的结构基础和分子机制。
内质网是细胞内承担蛋白质合成，脂类合成和钙离子存储等重要功能的细胞器，内质网的形态动态与其功能有着紧密的关联。2009年，胡俊杰等人在《Cell》发表文章，显示Atlastin蛋白家族参与了内质网管状网络的形成，可能直接诱导内质网管状结构之间的膜融合，他们还发现Atalsin突变导致的遗传性痉挛性截瘫与内质网的形态有着直接的联系。
在本项研究中，胡俊杰实验室的边鑫等人在刘新奇实验室的协助下，解析了Atlastin胞浆区结构域的晶体结构，发现了两种不同的构象，并通过生化实验验证了这些构象变化对膜融合的重要性，从而提出了一个生物膜融合的新机制，该项研究还解释了Atlastin众多点突变导致截瘫的分子基础。该工作得到了国家自然科学基金、科技部重大科学研究计划等项目的资助，同时，这也是一项体现青年研究人员优势互补，协同合作的成果。
此外，南开大学生命科学学院宁文教授的文章也已经被《PNAS》正式接受，并于近期发表。这也将是南开大学生命科学学院自2007年以来发表于《PNAS》的第6篇文章。（生物谷Bioon.com）
生物谷推荐原文出处：
PNAS doi: 10.1073/pnas.1101643108
Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes
Xin Biana,b,1, Robin W. Klemmc,1, Tina Y. Liuc,1, Miao Zhanga,b, Sha Suna,b, Xuewu Suia,b, Xinqi Liub,d,2, Tom A. Rapoportc,2, and Junjie Hua,b,2
The generation of the tubular network of the endoplasmic reticulum (ER) requires homotypic membrane fusion that is mediated by the dynamin-like, membrane-bound GTPase atlastin (ATL). Here, we have determined crystal structures of the cytosolic segment of human ATL1, which give insight into the mechanism of membrane fusion. The structures reveal a GTPase domain and athree-helix bundle, connected by a linker region. One structure corresponds to a prefusion state, in which ATL molecules in apposing membranes interact through their GTPase domains to form a dimer with the nucleotides bound at the interface. The other structure corresponds to a postfusion state generated after GTP hydrolysis and phosphate release. Compared with the prefusion structure, the three-helix bundles of the two ATL molecules undergo a major conformational change relative to the GTPase domains, which could pull the membranes together. The proposed fusion mechanism is supported by biochemical experiments and fusion assays with wild-type and mutant full-length Drosophila ATL. These experiments also show that membrane fusion is facilitated by the C-terminal cytosolic tails following the two transmembrane segments. Finally, our results show that mutations in ATL1 causing hereditary spastic paraplegia compromise homotypic ER fusion.
