A highly conserved hydrophobic motif in the exofacial vestibule of fructose transporting SLC2A proteins acts as a critical determinant of their substrate selectivity
A highly conserved hydrophobic motif in the exofacial vestibule of fructose transporting SLC2A proteins acts as a critical determinant of their substrate selectivity
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DOI：
10.1080/09687680701298143
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发表时间：
2007-01-01
影响因子：
--
通讯作者：
Cheeseman, Chris
中科院分区：
文献类型：
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作者：
Manolescu, Andrei R.;Augustin, Robert;Cheeseman, Chris
易化己糖转运蛋白 GLUT 家族（基因 SLC2A）的底物特异性差异很大。有些似乎能够转运葡萄糖和果糖，而处理 2-脱氧葡萄糖和半乳糖的能力并不一定与其他两种己糖相关。人们普遍认为，中心底物结合/易位位点决定了哪些己糖可以被运输。然而，最近的一项研究表明，GLUT 2、5 和 7 中疏水残基的单点突变消除了它们转运果糖的能力，而不影响葡萄糖渗透动力学。该残留物位于第七跨膜螺旋中，面向房水孔并靠近面外前庭的开口。这项研究将这些观察结果扩展到包括其他 II 类过剩（9 和 11），并表明三氨基酸基序（NXI/NXV）似乎对于确定果糖是否可以进入易位机制至关重要。 GLUT11 也可以转运果糖，但它在相同位置具有基序 DSV，其功能似乎与 NXI 相同，并且当所有三个残基都被 NAV 替换时，果糖转运就会丢失。讨论了这些结果与外表面前庭开口处水孔内衬的疏水残基的可能作用有关。最后，检查了易位结合位点可能不是这些蛋白质的底物特异性的唯一决定因素的可能性。
The substrate specificity of the facilitated hexose transporter, GLUT, family, ( gene SLC2A) is highly varied. Some appear to be able to translocate both glucose and fructose, while the ability to handle 2- deoxyglucose and galactose does not necessarily correlate with the other two hexoses. It has become generally accepted that a central substrate binding/ translocation site determines which hexoses can be transported. However, a recent study showed that a single point mutation of a hydrophobic residue in GLUTs 2, 5 & 7 removed their ability to transport fructose without affecting the kinetics of glucose permeation. This residue is in the 7th transmembrane helix, facing the aqueous pore and lies close to the opening of the exofacial vestibule. This study expands these observations to include the other class II GLUTs ( 9 & 11) and shows that a three amino acid motif ( NXI/ NXV) appears to be critical in determining if fructose can access the translocation mechanism. GLUT11 can also transport fructose, but it has the motif DSV at the same position, which appears to function in the same manner as NXI and when all three residues are replaced with NAV fructose transport lost. These results are discussed in relation to possible roles for hydrophobic residues lining the aqueous pore at the opening of the exofacial vestibule. Finally, the possibility that the translocation binding site may not be the sole determinant of substrate specificity for these proteins is examined.