日本一個(gè)研究小組在最新一期美國《科學(xué)》雜志上報(bào)告說,,他們探明了生物細(xì)胞內(nèi)一種大型蛋白質(zhì)“穹窿體”的構(gòu)造,,這將有助于開發(fā)效果更好的癌癥治療藥物等。
“穹窿體”是細(xì)胞內(nèi)已知最大的蛋白質(zhì)之一,,它與生物機(jī)體的免疫反應(yīng)以及耐藥性等相關(guān),,但具體形態(tài)一直不為人所知。日本兵庫縣立大學(xué),、大阪大學(xué)和北海道大學(xué)等高校的研究人員利用位于兵庫縣的大型同步輻射加速器Spring-8的強(qiáng)X射線照射這種蛋白質(zhì),,發(fā)現(xiàn)它由上下各39根、共計(jì)78根繩索狀的分子聚集在一起,編織成中空的竹籠形狀,。
研究人員推測,,在多種抗癌劑都不起作用的耐藥癌細(xì)胞內(nèi),抗癌劑被吸收到“穹窿體”蛋白質(zhì)中間的空洞后再排出細(xì)胞外,,導(dǎo)致癌細(xì)胞的耐藥性,。本次研究探明了“穹窿體”蛋白質(zhì)的構(gòu)造,將有助于今后開發(fā)效果更好的癌癥治療藥物等,。(生物谷Bioon.com)
生物谷推薦原始出處:
Science 16 January 2009: DOI: 10.1126/science.1164975
The Structure of Rat Liver Vault at 3.5 Angstrom Resolution
Hideaki Tanaka,1* Koji Kato,1* Eiki Yamashita,1 Tomoyuki Sumizawa,2 Yong Zhou,3 Min Yao,3 Kenji Iwasaki,1,4 Masato Yoshimura,5 Tomitake Tsukihara1,6
Vaults are among the largest cytoplasmic ribonucleoprotein particles and are found in numerous eukaryotic species. Roles in multidrug resistance and innate immunity have been suggested, but the cellular function remains unclear. We have determined the x-ray structure of rat liver vault at 3.5 angstrom resolution and show that the cage structure consists of a dimer of half-vaults, with each half-vault comprising 39 identical major vault protein (MVP) chains. Each MVP monomer folds into 12 domains: nine structural repeat domains, a shoulder domain, a cap-helix domain, and a cap-ring domain. Interactions between the 42-turn-long cap-helix domains are key to stabilizing the particle. The shoulder domain is structurally similar to a core domain of stomatin, a lipid-raft component in erythrocytes and epithelial cells.
1 Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
2 University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka 807-8555, Japan.
3 Faculty of Advanced Life Sciences, Graduate School of Life Sciences, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan.
4 Bio-multisome Research Team, Structural Physiology Research Group, RIKEN Harima Institute, Mikazuki Sayo, Hyogo 679-5148, Japan.
5 National Synchrotron Radiation Research Center, 101 Hsin-Ann Road, Hsinchu Science Park, Hsinchu 30076, Taiwan.
6 Department of Life Science, University of Hyogo, 3-2-1 Koto, Kamighori, Akoh, Hyogo 678-1297, Japan.