Leptin and leptin receptor: analysis of a structure to function relationship in interaction and evolution from humans to fish.
Leptin and leptin receptor: analysis of a structure to function relationship in interaction and evolution from humans to fish.
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DOI：
10.1016/j.peptides.2012.10.002
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发表时间：
2012-12
期刊：
影响因子：
3
通讯作者：
Londraville RL
中科院分区：
文献类型：
--
作者：
Prokop JW;Duff RJ;Ball HC;Copeland DL;Londraville RL
瘦素是一种循环蛋白，通过与瘦素受体结合来调节饮食摄入量。许多实验室已经使用已知的结构和突变来研究常见动物模型(人、小鼠和大鼠)的这种结合过程。了解其他脊椎动物的这种结合过程将有助于更好地了解瘦素及其受体的功能。瘦素和瘦素受体之间的结合位点在哺乳动物中是高度保守的，通过映射到瘦素和瘦素受体结构上的序列比对证实了这一点。在蜥蜴和青蛙的序列中，这种相互作用的变化更大。使用我们的模型，我们发现禽类瘦素序列在结合位置上的变异比瘦素受体的变异要小得多。这一分析进一步表明，禽类瘦素是人工合成的。在鱼类中，基因复制事件导致了多种瘦素蛋白的表达。这些多个瘦素蛋白在与瘦素受体相互作用的区域有变异。在斑马鱼和日本米鱼中，我们认为瘦素A具有比B更高的结合能。不同的结合能是瘦素B功能分化、结合确认不同或其他蛋白质伙伴的证据。
Leptin is a circulating protein which regulates dietary intake through binding the leptin receptor. Numerous labs have used known structures and mutagenesis to study this binding process in common animal models (human, mouse and rat). Understanding this binding process in other vertebrate species will allow for a better understanding of leptin and leptin receptor function. The binding site between leptin and leptin receptor is highly conserved in mammals as confirmed through sequence alignments mapped onto structures of both leptin and leptin receptor. More variation in this interaction is found in lizard and frog sequences. Using our models, we show that the avian leptin sequences have far less variation in the binding site than does the leptin receptor. This analysis further suggests that avian leptins are artifactual. In fish, gene duplication events have led to the expression of multiple leptin proteins. These multiple leptin proteins have variation in the regions interacting with leptin receptor. In zebrafish and the Japanese rice fish, we propose that leptin A has a higher binding energy than does B. Differing binding energies are evidence of either divergent functions, different binding confirmations, or other protein partners of leptin B.
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DOI：
10.1093/bioinformatics/8.3.275
发表时间：
1992-06-01
期刊：
COMPUTER APPLICATIONS IN THE BIOSCIENCES
影响因子：
--
作者：
JONES, DT;TAYLOR, WR;THORNTON, JM
通讯作者：
THORNTON, JM
影响因子：
4
作者：
Gorissen, Marnix;Bernier, Nicholas J.;Huising, Mark O.
通讯作者：
Huising, Mark O.
DOI：
10.1073/pnas.95.11.6061
发表时间：
1998-05-26
影响因子：
11.1
作者：
Carpenter, LR;Farruggella, TJ;Stahl, N
通讯作者：
Stahl, N
影响因子：
2.7
作者：
Friedman-Einat, M;Boswell, T;Sharp, PJ
通讯作者：
Sharp, PJ
影响因子：
3
作者：
Duan, Y;Wu, C;Kollman, P
通讯作者：
Kollman, P