为探究脯氨酸(Proline,Pro)、谷氨酸(Glutamic Acid,Glu)二肽与鲜味受体分子相互作用,该研究合成了12个Pro、Glu二肽,以感官评价为基础,利用同源建模、分子对接技术研究Pro、Glu二肽与味觉受体第一家族亚型1(Taste Receptor Type 1 Memb...为探究脯氨酸(Proline,Pro)、谷氨酸(Glutamic Acid,Glu)二肽与鲜味受体分子相互作用,该研究合成了12个Pro、Glu二肽,以感官评价为基础,利用同源建模、分子对接技术研究Pro、Glu二肽与味觉受体第一家族亚型1(Taste Receptor Type 1 Member 1,T1R1)、味觉受体第一家族亚型3(Taste Receptor Type 1 Member 3,T1R3)和钙敏感受体(Calcium Sensitive Receptor,CaSR)的构效关系。结果表明:除脯氨酸-丝氨酸(Proline-serine,Pro-Ser)、缬氨酸-脯氨酸(Valine-proline,Val-Pro)和亮氨酸-谷氨酸(Leucine-glutamic Acid,Leu-Glu)不呈鲜,其余二肽的呈鲜阈值均低于谷氨酸钠阈值(0.3 mg/mL),其中γ-谷氨酸-蛋氨酸(γ-Glutamic Acid-methionine,γ-Glu-Met)和甘氨酸-谷氨酸(Glycine-glutamic Acid,Gly-Glu)的呈鲜阈值最低,为0.07 mg/mL。二肽与T1R1的关键结合位点为Asp147、Thr149、Ser172和Arg277,T1R1是Glu二肽呈鲜的重要受体;与T1R3的关键结合位点为Glu45、Ser147、Val277和His278,Ser147是N-γ-Glu二肽与T1R3受体的关键结合位点;与CaSR的关键结合位点为Leu173、Asn176、Gln179、Arg220、Ser244和Asp275,Glu二肽比Pro二肽更易与CaSR受体结合。二肽与受体主要通过氢键与疏水相互作用结合,呈味较强的二肽在对接时多嵌于受体结合口袋深处;呈味较弱的二肽有的位于结合口袋较浅的位置,有的其疏水区或亲水区暴露于受体表面。该研究有助于阐明鲜味肽与鲜味受体相互作用机制,为深入研究鲜味肽呈鲜机理奠定基础。展开更多
Adaptive evolution plays a role in the functional divergence and specialization of taste receptors and the sense of taste is thought to be closely related to feeding ecology.To examine whether feeding ecology has shap...Adaptive evolution plays a role in the functional divergence and specialization of taste receptors and the sense of taste is thought to be closely related to feeding ecology.To examine whether feeding ecology has shaped the evolution of taste receptor genes in vertebrates,we here focus on Tas1r gene family that encodes umami(Tas1r1 and Tas1r3 heterodimer) and sweet(Tas1r2 and Tas1r3 heterodimer) taste receptors.By searching currently available genome sequences in 48 vertebrates that contain 38 mammals,1 reptile,3 birds,1 frog,and 5 fishes,we found all three members of Tas1rs are intact in most species,suggesting umami and sweet tastes are maintained in most vertebrates.Interestingly,the absence and pseudogenization of Tas1rs were also discovered in a number of species with diverse feeding preferences and distinct phylogenetic positions,indicating widespread losses of umami and/or sweet tastes in these animals,irrespective of their diet.Together with previous findings showing losses of tastes in other vertebrates,we failed to identify common dietary factors that could result in the taste losses.Our results report here suggest the evolution of Tas1rs is more complex than we previously appreciated and highlight the caveat of analyzing sequences predicted from draft genome sequences.Future work for a better understanding of taste receptor function would help uncover what ecological factors have driven the evolution history of Tas1rs in vertebrates.展开更多
文摘为探究脯氨酸(Proline,Pro)、谷氨酸(Glutamic Acid,Glu)二肽与鲜味受体分子相互作用,该研究合成了12个Pro、Glu二肽,以感官评价为基础,利用同源建模、分子对接技术研究Pro、Glu二肽与味觉受体第一家族亚型1(Taste Receptor Type 1 Member 1,T1R1)、味觉受体第一家族亚型3(Taste Receptor Type 1 Member 3,T1R3)和钙敏感受体(Calcium Sensitive Receptor,CaSR)的构效关系。结果表明:除脯氨酸-丝氨酸(Proline-serine,Pro-Ser)、缬氨酸-脯氨酸(Valine-proline,Val-Pro)和亮氨酸-谷氨酸(Leucine-glutamic Acid,Leu-Glu)不呈鲜,其余二肽的呈鲜阈值均低于谷氨酸钠阈值(0.3 mg/mL),其中γ-谷氨酸-蛋氨酸(γ-Glutamic Acid-methionine,γ-Glu-Met)和甘氨酸-谷氨酸(Glycine-glutamic Acid,Gly-Glu)的呈鲜阈值最低,为0.07 mg/mL。二肽与T1R1的关键结合位点为Asp147、Thr149、Ser172和Arg277,T1R1是Glu二肽呈鲜的重要受体;与T1R3的关键结合位点为Glu45、Ser147、Val277和His278,Ser147是N-γ-Glu二肽与T1R3受体的关键结合位点;与CaSR的关键结合位点为Leu173、Asn176、Gln179、Arg220、Ser244和Asp275,Glu二肽比Pro二肽更易与CaSR受体结合。二肽与受体主要通过氢键与疏水相互作用结合,呈味较强的二肽在对接时多嵌于受体结合口袋深处;呈味较弱的二肽有的位于结合口袋较浅的位置,有的其疏水区或亲水区暴露于受体表面。该研究有助于阐明鲜味肽与鲜味受体相互作用机制,为深入研究鲜味肽呈鲜机理奠定基础。
基金supported by a start-up fund from Wuhan University to H. Z
文摘Adaptive evolution plays a role in the functional divergence and specialization of taste receptors and the sense of taste is thought to be closely related to feeding ecology.To examine whether feeding ecology has shaped the evolution of taste receptor genes in vertebrates,we here focus on Tas1r gene family that encodes umami(Tas1r1 and Tas1r3 heterodimer) and sweet(Tas1r2 and Tas1r3 heterodimer) taste receptors.By searching currently available genome sequences in 48 vertebrates that contain 38 mammals,1 reptile,3 birds,1 frog,and 5 fishes,we found all three members of Tas1rs are intact in most species,suggesting umami and sweet tastes are maintained in most vertebrates.Interestingly,the absence and pseudogenization of Tas1rs were also discovered in a number of species with diverse feeding preferences and distinct phylogenetic positions,indicating widespread losses of umami and/or sweet tastes in these animals,irrespective of their diet.Together with previous findings showing losses of tastes in other vertebrates,we failed to identify common dietary factors that could result in the taste losses.Our results report here suggest the evolution of Tas1rs is more complex than we previously appreciated and highlight the caveat of analyzing sequences predicted from draft genome sequences.Future work for a better understanding of taste receptor function would help uncover what ecological factors have driven the evolution history of Tas1rs in vertebrates.
