2011年新學(xué)期伊始，國際重要學(xué)術(shù)期刊 Proceedings of the National Academy of Sciences 在線發(fā)表了南開大學(xué)生命科學(xué)學(xué)院胡俊杰和劉新奇課題組合作的最新研究成果,，該成果揭示了嵌膜GTP酶Atlastin介導(dǎo)內(nèi)質(zhì)網(wǎng)膜融合的結(jié)構(gòu)基礎(chǔ)和分子機(jī)制,。
內(nèi)質(zhì)網(wǎng)是細(xì)胞內(nèi)承擔(dān)蛋白質(zhì)合成，脂類合成和鈣離子存儲等重要功能的細(xì)胞器,，內(nèi)質(zhì)網(wǎng)的形態(tài)動態(tài)與其功能有著緊密的關(guān)聯(lián),。2009年，胡俊杰等人在《Cell》發(fā)表文章,，顯示Atlastin蛋白家族參與了內(nèi)質(zhì)網(wǎng)管狀網(wǎng)絡(luò)的形成,，可能直接誘導(dǎo)內(nèi)質(zhì)網(wǎng)管狀結(jié)構(gòu)之間的膜融合，他們還發(fā)現(xiàn)Atalsin突變導(dǎo)致的遺傳性痙攣性截癱與內(nèi)質(zhì)網(wǎng)的形態(tài)有著直接的聯(lián)系,。
在本項研究中,，胡俊杰實驗室的邊鑫等人在劉新奇實驗室的協(xié)助下，解析了Atlastin胞漿區(qū)結(jié)構(gòu)域的晶體結(jié)構(gòu),，發(fā)現(xiàn)了兩種不同的構(gòu)象,，并通過生化實驗驗證了這些構(gòu)象變化對膜融合的重要性，從而提出了一個生物膜融合的新機(jī)制,，該項研究還解釋了Atlastin眾多點突變導(dǎo)致截癱的分子基礎(chǔ),。該工作得到了國家自然科學(xué)基金、科技部重大科學(xué)研究計劃等項目的資助,，同時,，這也是一項體現(xiàn)青年研究人員優(yōu)勢互補(bǔ),，協(xié)同合作的成果。
此外,，南開大學(xué)生命科學(xué)學(xué)院寧文教授的文章也已經(jīng)被《PNAS》正式接受,，并于近期發(fā)表。這也將是南開大學(xué)生命科學(xué)學(xué)院自2007年以來發(fā)表于《PNAS》的第6篇文章,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
