REVERSIBLE UNFOLDING OF FIBRONECTIN TYPE-III AND IMMUNOGLOBULIN DOMAINS PROVIDES THE STRUCTURAL BASIS FOR STRETCH AND ELASTICITY OF TITIN AND FIBRONECTIN
REVERSIBLE UNFOLDING OF FIBRONECTIN TYPE-III AND IMMUNOGLOBULIN DOMAINS PROVIDES THE STRUCTURAL BASIS FOR STRETCH AND ELASTICITY OF TITIN AND FIBRONECTIN
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DOI：
10.1073/pnas.91.21.10114
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发表时间：
1994-10-11
影响因子：
11.1
通讯作者：
ERICKSON, HP
中科院分区：
文献类型：
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作者：
ERICKSON, HP
弹性蛋白titin由纤维连接蛋白III型和免疫球蛋白结构域组成的串联阵列，它们在结构上是相似的7链β-三明治。本文定量分析了Titin拉伸的一种机制，该机制是通过对单个纤维连接蛋白III型免疫球蛋白结构域的顺序变性来响应外加的张力。折叠的结构域大约有4 nm长，解开的多肽可以延伸到29 nm，在松弛的长度上提供7倍的拉伸。弹性反冲是通过当力释放时变性磁区的重新折叠来实现的。根据7-14千卡/摩尔的变性净自由能加上5千卡/摩尔的延伸多肽(1cal=4.184 J)，计算出变性结构域所需的临界力为3.5pN-5pN。这种作用力与单个肌球蛋白或动蛋白分子产生的2-7-pN的作用力相当。在这里，拉开非共价蛋白质-蛋白质界面所需的力估计为10-30pN，这意味着在分子从Z带的附着位置拉出之前，Titin将在内部拉伸。许多细胞外基质和细胞黏附分子，如纤维连接蛋白，含有纤维连接蛋白III型结构域的串联阵列。单分子和基质纤维都应该具有与Titin类似的弹性特性。
The elastic protein titin comprises a tandem array of fibronectin type III and immunoglobulin domains, which are structurally similar 7-strand beta-sandwiches. A proposed mechanism for stretching titin, by sequential denaturation of individual fibronectin type III-immunoglobulin domains in response to applied tension, is analyzed here quantitatively. The folded domain is approximate to 4 nm long, and the unraveled polypeptide can extend to 29 nm, providing a 7-fold stretch over the relaxed length. Elastic recoil is achieved by refolding of the denatured domains when the force is released. The critical force required to denature a domain is calculated to be 3.5-5 pN, based on a net free energy for denaturation of 7-14 kcal/mol, plus 5 kcal/mol to extend the polypeptide (1 cal = 4.184 J). This force is comparable to the 2- to 7-pN force generated by single myosin or kinesin molecules. The force needed to pull apart a noncovalent protein-protein interface is estimated here to be 10-30 pN, implying that titin will stretch internally before the molecule is pulled from its attachment at the Z band. Many extracellular matrix and cell adhesion molecules, such as fibronectin, contain tandem arrays of fibronectin type III domains. Both single molecules and matrix fibers should have elastic properties similar to titin.