4.6 Article

Tying up the Loose Ends: A Mathematically Knotted Protein

期刊

FRONTIERS IN CHEMISTRY
卷 9, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fchem.2021.663241

关键词

Knotted proteins; NMR spectrocopy; protein trans-splicing; enzymatic ligation; protein dynamics; protein stability and folding

资金

  1. Ministry of Science and Technology, Taiwan [105-2113-M-001-005, 106-2113-M-001004, 107-2628-M-001-005-MY3]
  2. Academia Sinica, Taiwan
  3. Sigrid Juselius Foundation
  4. Academy of Finland [131413, 137995, 277335, 308239]
  5. National Research Council of Taiwan
  6. Helsinki University Library
  7. Academy of Finland (AKA) [308239, 308239] Funding Source: Academy of Finland (AKA)

向作者/读者索取更多资源

The topology of protein structures has a significant impact on their function and physicochemical properties, with differences between backbone cyclization and structural topology affecting protein characteristics.
Knots have attracted scientists in mathematics, physics, biology, and engineering. Long flexible thin strings easily knot and tangle as experienced in our daily life. Similarly, long polymer chains inevitably tend to get trapped into knots. Little is known about their formation or function in proteins despite >1,000 knotted proteins identified in nature. However, these protein knots are not mathematical knots with their backbone polypeptide chains because of their open termini, and the presence of a knot depends on the algorithm used to create path closure. Furthermore, it is generally not possible to control the topology of the unfolded states of proteins, therefore making it challenging to characterize functional and physicochemical properties of knotting in any polymer. Covalently linking the amino and carboxyl termini of the deeply trefoil-knotted YibK from Pseudomonas aeruginosa allowed us to create the truly backbone knotted protein by enzymatic peptide ligation. Moreover, we produced and investigated backbone cyclized YibK without any knotted structure. Thus, we could directly probe the effect of the backbone knot and the decrease in conformational entropy on protein folding. The backbone cyclization did not perturb the native structure and its cofactor binding affinity, but it substantially increased the thermal stability and reduced the aggregation propensity. The enhanced stability of a backbone knotted YibK could be mainly originated from an increased ruggedness of its free energy landscape and the destabilization of the denatured state by backbone cyclization with little contribution from a knot structure. Despite the heterogeneity in the side-chain compositions, the chemically unfolded cyclized YibK exhibited several macroscopic physico-chemical attributes that agree with theoretical predictions derived from polymer physics.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据