A DESIGNED METAL-BINDING PROTEIN WITH A NOVEL FOLD

被引:185
作者
PESSI, A
BIANCHI, E
CRAMERI, A
VENTURINI, S
TRAMONTANO, A
SOLLAZZO, M
机构
[1] IST RIC BIOL MOLEC P ANGELETTI, DEPT GENET, VIA PONTINA KM 306, I-00040 POMEZIA, ITALY
[2] IST RIC BIOL MOLEC P ANGELETTI, DEPT BIOCHEM, I-00040 POMEZIA, ITALY
[3] IST RIC BIOL MOLEC P ANGELETTI, DEPT BIOCOMP, I-00040 POMEZIA, ITALY
关键词
D O I
10.1038/362367a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A MAJOR challenge in protein design is to create stable scaffolds into which tailored functions can be introduced. Here we present the design, synthesis and characterization of a 61-residue all-beta protein: the minibody. We used a portion of the heavy chain variable domain of an immunoglobulin as a template, obtaining a molecule with a novel beta-sheet scaffold and two regions corresponding to the hypervariable loops H1 and H2. To exploit the potential for creating functional centres in the minibody, we engineered a metal-binding site into it. This site is formed by one histidine in H1 and two in H2. The protein is folded, compact and able to bind metal, thus representing the first designed beta-protein with a novel fold and a tailored function. By randomizing the sequence of the hypervariable loops, we are using the minibody scaffold to construct a conformationally constrained peptide library displayed on phage.
引用
收藏
页码:367 / 369
页数:3
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