Identification of the receptor-recognition surface of bombyxin-II, an insulin-like peptide of the silkmoth Bombyx mori: critical importance of the B-chain central part.
Identification of the receptor-recognition surface of bombyxin-II, an insulin-like peptide of the silkmoth Bombyx mori: critical importance of the B-chain central part.
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DOI：
10.1006/jmbi.1995.0589
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发表时间：
1995-11
影响因子：
5.6
通讯作者：
K. Nagata;H. Hatanaka;D. Kohda;H. Kataoka;H. Nagasawa;A. Isogai;H. Ishizaki;A. Suzuki;F. Inagaki
中科院分区：
文献类型：
--
作者：
K. Nagata;H. Hatanaka;D. Kohda;H. Kataoka;H. Nagasawa;A. Isogai;H. Ishizaki;A. Suzuki;F. Inagaki
家蚕胰岛素-Ⅱ是家蚕脑内分泌肽，与人胰岛素有40%的同源性，其特征性核心结构与人胰岛素相似。尽管结构相似，但它们之间没有观察到交叉活性。为了定位Bombyxin-II的活性区域，我们合成了Bombyxin-II和人胰岛素的嵌合分子，并检测了它们的Bombyxin活性。两个嵌合分子，这是顺序相同的，除了B链的中心部分，显示出显着不同的效力，在蚕毒素活性。这些嵌合分子的溶液结构测定表明，它们的B链中心部分采取类似的主链构象，但形成不同的补丁在其分子表面。因此，由家蚕毒素-II B链的中心部分形成的表面补丁对于识别家蚕毒素受体至关重要。上述结果与其它有关家蚕毒素构效关系的数据表明，家蚕毒素-Ⅱ的受体识别表面除B链中心部分外，还包括A链的N端和C端。虽然蚕毒素-II、人胰岛素和人松弛素2使用共同的表面作为它们的受体识别位点，但每个表面补丁的特征在于所涉及的侧链的多样性。胰岛素和松弛素涉及受体识别的额外部分，特别是分别为B链C-末端部分和延伸的A链N-末端螺旋。总之，这些配体在保留主要识别表面的同时，进化出了它们自己的受体识别特异性机制。
Bombyxin-II, a brain-secretory peptide of the silkmoth Bombyx mori, shares 40% sequence identify and the characteristics core structure with human insulin. In spite of the structural similarity, no cross-activity is observed between them. To localize the active region of bombyxin-II, we have synthesized chimeric molecules of bombyxin-II and human insulin, and examined their bombyxin activity. Two chimeric molecules, which were sequentially identical except for the B-chain central part, showed significantly different potencies in bombyxin activity. Solution structure determination of these chimeric molecules revealed that their B-chain central parts took similar main-chain conformation, but formed dissimilar patches on their molecular surfaces. Therefore, the surface patch formed by the central part of the bombyxin-II B-chain is of critical importance for recognition of the bombyxin receptor. The above results, together with other data on the structure-activity relationships of bombyxin, indicate that the receptor-recognition surface of bombyxin-II includes the A-chain N and C, termini in addition to the B-chain central part. Though bombyxin-II, human insulin and human relaxin 2 use the common surface as their receptor-recognition sites, each of the surface patches is characterized by the variety of involved side-chains. Insulin and relaxin involve additional parts for receptor recognition, particularly the B-chain C-terminal part and the extended A-chain N-terminal helix, respectively. In conclusion, these ligands have evolved their own specific mechanisms for receptor recognition while retaining the major recognition surface.