日本一个研究小组在最新一期美国《科学》杂志上报告说,他们探明了生物细胞内一种大型蛋白质“穹窿体”的构造,这将有助于开发效果更好的癌症治疗药物等。
“穹窿体”是细胞内已知最大的蛋白质之一,它与生物机体的免疫反应以及耐药性等相关,但具体形态一直不为人所知。日本兵库县立大学、大阪大学和北海道大学等高校的研究人员利用位于兵库县的大型同步辐射加速器Spring-8的强X射线照射这种蛋白质,发现它由上下各39根、共计78根绳索状的分子聚集在一起,编织成中空的竹笼形状。
研究人员推测,在多种抗癌剂都不起作用的耐药癌细胞内,抗癌剂被吸收到“穹窿体”蛋白质中间的空洞后再排出细胞外,导致癌细胞的耐药性。本次研究探明了“穹窿体”蛋白质的构造,将有助于今后开发效果更好的癌症治疗药物等。(生物谷Bioon.com)
生物谷推荐原始出处:
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.