雷帕霉素靶蛋白的结构域和重复结构的研究进展
Insights into the domain and repeat architecture of target of rapamycin.
机构信息
Fred Hutchinson Cancer Research Center, Basic Sciences Division, 1100 Fairview Ave N, P.O. Box 19024, Mailstop A1-162, Seattle, WA 98109, USA.
出版信息
J Struct Biol. 2010 May;170(2):354-63. doi: 10.1016/j.jsb.2010.01.002. Epub 2010 Jan 11.
Abstract
A simple and efficient protein sequence analysis strategy was developed to predict the number and location of structural repeats in the TOR protein. This strategy uses multiple HHpred alignments against proteins of known 3D structure to enable protein repeats referenced from the 3D structure to be traced back to the query protein sequence by using user-directed repeat assignments. The HHpred strategy performed with high sensitivity by predicting 100% of the repeat units within a test set of HEAT- and TPR-repeat-containing proteins of known three-dimensional structure. The HHpred strategy predicts that TOR contains 32 tandem HEAT repeats extending from the N-terminus to the FAT domain, which is itself comprised of 16 tandem TPR repeats. These findings were used to assemble a 3D atomic model for the TOR protein.
摘要
我们开发了一种简单而高效的蛋白质序列分析策略，用于预测 TOR 蛋白中结构重复的数量和位置。该策略使用多个 HHpred 比对已知 3D 结构的蛋白质，通过用户指导的重复分配，使来自 3D 结构的蛋白质重复能够追溯到查询蛋白质序列。HHpred 策略通过预测已知三维结构的 HEAT 和 TPR 重复蛋白测试集中的重复单元，达到了 100%的敏感性。HHpred 策略预测 TOR 包含 32 个串联 HEAT 重复，从 N 端延伸到 FAT 结构域，而 FAT 结构域本身由 16 个串联 TPR 重复组成。这些发现被用于组装 TOR 蛋白的 3D 原子模型。
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1
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PLoS One. 2009 Sep 24;4(9):e7148. doi: 10.1371/journal.pone.0007148.
2
Evolutionary constraints on structural similarity in orthologs and paralogs.直系同源基因和旁系同源基因结构相似性的进化限制。
Protein Sci. 2009 Jun;18(6):1306-15. doi: 10.1002/pro.143.
3
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PLoS Comput Biol. 2009 Mar;5(3):e1000304. doi: 10.1371/journal.pcbi.1000304. Epub 2009 Mar 13.
4
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Biochem Soc Trans. 2009 Feb;37(Pt 1):259-64. doi: 10.1042/BST0370259.
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Nucleic Acids Res. 2009 Jan;37(Database issue):D387-92. doi: 10.1093/nar/gkn750. Epub 2008 Oct 18.
6
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