片說明：科學家畫出的細胞外基質(zhì)受體糖蛋白,，一種跨膜蛋白,。紅色表示ß亞基,，藍色表示α亞基和較小的人造多肽。
( 生物谷配圖)
更多生物圖片請進入
蛋白質(zhì)是生物體的重要組成部分,，大約有三分之一的蛋白質(zhì)是存在于細胞膜中的膜蛋白,。科學家很容易利用抗體等對其他三分之二的蛋白質(zhì)進行研究,，但對于膜蛋白,，情況就要復雜得多。
為了探測這些似乎“無法接近”的蛋白質(zhì),，美國賓西法尼亞大學（University of Pennsylvania）醫(yī)學院的研究人員利用計算機技術和已知的蛋白質(zhì)結(jié)構(gòu)信息,，設計制造出一些多肽，它們能夠“綁定”相關跨膜蛋白（transmembrane protein）的特定區(qū)域,，從而使科學家研究了細胞外基質(zhì)受體糖蛋白（integrin）對凝血過程第一步的影響機制,。該研究成果發(fā)表在3月30日《科學》雜志上。
科學家集中研究了兩種名為αIIbß3和αvß3的細胞外基質(zhì)受體糖蛋白,，它們都是會影響凝血時血小板作用的跨膜蛋白,。論文高級作者之一、醫(yī)學教授Joel Bennett表示,，“我們想看看利用兩種不同的多肽能否區(qū)分出這兩種跨膜蛋白分別的作用……事實上,，我們做到了。”
當設計出的多肽被插入血小板細胞膜后,，它們與對應細胞外基質(zhì)受體糖蛋白的部分區(qū)域結(jié)合,，并對其在凝血過程中的官能產(chǎn)生擾動，從而使科學家能夠找到人體調(diào)控膜蛋白導致凝血的機制,。
Bennett表示,，將這種方法用于治療研究還有很長的路要走，但是科學家可以借此了解人體內(nèi)最基本的相互作用——細胞協(xié)作產(chǎn)生必需功能的方式,。而這些知識無疑將成為未來新的靶向藥物開發(fā)的基礎,。
部分英文原文：
Science 30 March 2007:
Vol. 315. no. 5820, pp. 1817 - 1822
DOI: 10.1126/science.1136782
Research Articles
Computational Design of Peptides That Target Transmembrane Helices
Hang Yin,1* Joanna S. Slusky,1* Bryan W. Berger,1 Robin S. Walters,1 Gaston Vilaire,2 Rustem I. Litvinov,3 James D. Lear,1 Gregory A. Caputo,1 Joel S. Bennett,2 William F. DeGrado1,4
A variety of methods exist for the design or selection of antibodies and other proteins that recognize the water-soluble regions of proteins; however, companion methods for targeting transmembrane (TM) regions are not available. Here, we describe a method for the computational design of peptides that target TM helices in a sequence-specific manner. To illustrate the method, peptides were designed that specifically recognize the TM helices of two closely related integrins (IIbß3 and vß3) in micelles, bacterial membranes, and mammalian cells. These data show that sequence-specific recognition of helices in TM proteins can be achieved through optimization of the geometric complementarity of the target-host complex.
1 Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Hematology-Oncology Division, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Department of Cell and Developmental Biology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4 Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: [email protected]
