Obtaining crystals and improving crystal quality are the two major tasks in protein crystallization methodology. In order to fulfil these tasks, structure biologists have developed a lot of methods for protein crystallization. The methods of molecular modification, including point mutations, reductive methylation, truncations and deletions, fusion protein, complexes cocrystallization, and in-situ proteolysis, have been used to change the crystallization properties of proteins. These techniques are capable of increasing the success rate of crystallization and improving the quality of crystals. With the increasing of the successful cases, molecular modification has become more and more important for protein structure determination. It is an invaluable method especially for the proteins that are hard to crystallize or obtain high quality crystals. The utilization of molecular modification in protein crystallization in recent years is reviewed. And the application prospects of this method are also presented.%获得晶体及提高晶体质量是蛋白质结晶方法学中的两大基本问题.为解决这两个问题,结构生物学家已发展了许多方法,其中针对蛋白质本身进行分子改造是非常重要的方法之一.通过蛋白质工程技术,如定点突变、还原甲基化修饰、剪切或删除构象柔性环区、融合蛋白、复合物共结晶、原位蛋白质水解等方法对蛋白质本身进行分子改造,可明显提高其结晶成功率及晶体质量.随着该方面成功案例的不断积累,分子改造技术越来越凸显出其在蛋白质结构解析中的重要作用,特别是对一些难以结晶或提高晶体质量的蛋白质而言,其应用价值更不可忽视.针对近年来分子改造技术在蛋白质结晶中的应用进行了回顾与总结,并展望了其未来的发展.
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