Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family.
Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family.
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DOI：
10.26508/lsa.202000858
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发表时间：
2021-04
影响因子：
4.4
通讯作者：
Pedersen BP
中科院分区：
文献类型：
--
作者：
Custódio TF;Paulsen PA;Frain KM;Pedersen BP
与GLUT 3相比，GLUT 1的新结构可以解释底物亲和力差异，并为定义通用糖波特家族的关键结构基序提供功能原理。人葡萄糖转运蛋白GLUT 1和GLUT 3作为糖转运蛋白（SP）家族的典型成员在葡萄糖摄取中发挥核心作用。GLUT 1和GLUT 3共享具有相同底物配位的完全保守的底物结合位点，但在与其生理功能一致的转运亲和力方面显着不同。在这里，我们提出了一个2.4纳米晶体结构的GLUT 1在一个向内开放的构象，并比较它与GLUT 3使用结构和功能数据。我们的工作表明，胞质“SP基序”和保守的“A基序”之间的相互作用稳定了外向构象状态，并增加了底物表观亲和力。此外，我们确定了一个以前未描述的Cl−离子网站GLUT 1和内面脂质/葡萄糖结合位点，调节GLUT动力学。这些结果为GLUT 1和GLUT 3葡萄糖亲和力之间的差异提供了可能的解释，暗示了GLUTs动力学调节的一般模型，并暗示了SP家族中定义SP序列基序的生理功能。
A new structure of GLUT1, compared with GLUT3, can explain substrate affinity differences, and provide a functional rationale for key structural motifs that define the universal Sugar Porter family. The human glucose transporters GLUT1 and GLUT3 have a central role in glucose uptake as canonical members of the Sugar Porter (SP) family. GLUT1 and GLUT3 share a fully conserved substrate-binding site with identical substrate coordination, but differ significantly in transport affinity in line with their physiological function. Here, we present a 2.4 Å crystal structure of GLUT1 in an inward open conformation and compare it with GLUT3 using both structural and functional data. Our work shows that interactions between a cytosolic “SP motif” and a conserved “A motif” stabilize the outward conformational state and increases substrate apparent affinity. Furthermore, we identify a previously undescribed Cl− ion site in GLUT1 and an endofacial lipid/glucose binding site which modulate GLUT kinetics. The results provide a possible explanation for the difference between GLUT1 and GLUT3 glucose affinity, imply a general model for the kinetic regulation in GLUTs and suggest a physiological function for the defining SP sequence motif in the SP family.
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影响因子：
64.8
作者：
Nomura N;Verdon G;Kang HJ;Shimamura T;Nomura Y;Sonoda Y;Hussien SA;Qureshi AA;Coincon M;Sato Y;Abe H;Nakada-Nakura Y;Hino T;Arakawa T;Kusano-Arai O;Iwanari H;Murata T;Kobayashi T;Hamakubo T;Kasahara M;Iwata S;Drew D
通讯作者：
Drew D
影响因子：
5.5
作者：
Leduc-Nadeau, Alexandre;Lahjouji, Karim;Bichet, Daniel G.
通讯作者：
Bichet, Daniel G.
影响因子：
4.1
作者：
Maher, F;DaviesHill, TM;Simpson, IA
通讯作者：
Simpson, IA
影响因子：
3.5
作者：
Bentley, P. A.;Shao, Y.;Zhao, F. -Q.
通讯作者：
Zhao, F. -Q.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH