The Interaction between the Third Type III Domain from Fibronectin and Anastellin Involves β-Strand Exchange.
The Interaction between the Third Type III Domain from Fibronectin and Anastellin Involves β-Strand Exchange.
复制标题
纤连蛋白和 Anastellin 的第三个 III 型结构域之间的相互作用涉及 β 链交换。
DOI：
10.1021/acs.biochem.7b00633
复制
发表时间：
2017
期刊：
影响因子：
2.9
通讯作者：
Briknarová,Klára
中科院分区：
文献类型：
--
作者：
Stine,JessicaM;Ahl,GabrielJH;Schlenker,Casey;Rusnac,Domnita-Valeria;Briknarová,Klára
Anastellin is a small recombinant fragment derived from the extracellular matrix protein fibronectin; it comprises the first type III (FN3) domain without the two N-terminal β-strands. It inhibits angiogenesis, tumor growth, and metastasis in mouse models and requires endogenous fibronectin for itsin vivoanti-angiogenic activity. It binds to fibronectinin vitroand converts the soluble protein to insoluble fibrils that structurally and functionally resemble fibronectin fibrils deposited in the extracellular matrix by cells. Anastellin binds to several FN3 domains in fibronectin, but how it interacts with these domains and why the interactions lead to aggregation of fibronectin are not well understood. In this work, we investigated the interaction between anastellin and the third FN3 domain (3FN3) from fibronectin. We show that anastellin binds with high affinity to a peptide comprising the two N-terminal β-strands from 3FN3, and we present here the structure of the resulting complex. The peptide and anastellin form a composite FN3 domain, with the two N-terminal β-strands from 3FN3 bound in place of the two β-strands that are missing in anastellin. We also demonstrate using disulfide cross-linking that a similar interaction involving the two N-terminal β-strands of 3FN3 occurs when intact 3FN3 binds to anastellin. 3FN3 adopts a compact globular fold in solution, and to interact with anastellin in a manner consistent with our data, it has to open up and expose a β-strand edge that is not accessible in the context of the folded domain.
