Structural hot spots for the solubility of globular proteins

被引：57

作者：

Ganesan, Ashok ^{[1
,2
]}

Siekierska, Aleksandra ^{[1
,2
]}

Beerten, Jacinte ^{[1
,2
,3
]}

Brams, Marijke ^{[4
]}

Van Durme, Joost ^{[1
,3
]}

De Baets, Greet ^{[1
,2
]}

Van der Kant, Rob ^{[1
,2
]}

Gallardo, Rodrigo ^{[1
,2
]}

Ramakers, Meine ^{[1
,2
]}

Langenberg, Tobias ^{[1
,2
]}

Wilkinson, Hannah ^{[1
,2
]}

De Smet, Frederik ^{[1
,2
]}

Ulens, Chris ^{[4
]}

Rousseau, Frederic ^{[1
,2
]}

Schymkowitz, Joost ^{[1
,2
]}

机构：

[1] Flanders Inst Biotechnol VIB, VIB Switch Lab, B-3000 Leuven, Belgium

[2] Katholieke Univ Leuven, Switch Lab, Dept Cellular & Mol Med, Herestr 49,PB 802, B-3000 Leuven, Belgium

[3] Vrije Univ Brussel, Pl Laan 2, B-1050 Brussels, Belgium

[4] Katholieke Univ Leuven, Lab Struct Neurobiol, Dept Cellular & Mol Med, Herestr 49,PB 601, B-3000 Leuven, Belgium

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

欧洲研究理事会;

关键词：

PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; EXPRESSION LEVELS; MOLECULAR-BASIS; AGGREGATION; FORCE; PREVENTION; MUTATIONS; STABILITY; ABUNDANCE;

D O I：

10.1038/ncomms10816

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：

Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher protein concentrations are often problematic. This raises the question whether the solubility of natural protein sequences can be improved. We here show an anti-correlation between the number of aggregation prone regions (APRs) in a protein sequence and its solubility, suggesting that mutational suppression of APRs provides a simple strategy to increase protein solubility. We show that mutations at specific positions within a protein structure can act as APR suppressors without affecting protein stability. These hot spots for protein solubility are both structure and sequence dependent but can be computationally predicted. We demonstrate this by reducing the aggregation of human alpha-galactosidase and protective antigen of Bacillus anthracis through mutation. Our results indicate that many proteins possess hot spots allowing to adapt protein solubility independently of structure and function.

引用

页数：15

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