Lee John K, Khademi Shahram, Harries William, Savage David, Miercke Larry, Stroud Robert M
Department of Biochemistry and Biophysics, School of Medicine, University of California, San Francisco, CA 94143-2240, USA.
J Synchrotron Radiat. 2004 Jan 1;11(Pt 1):86-8. doi: 10.1107/s0909049503023872. Epub 2003 Nov 28.
The 2.2 A resolution crystal structure of GlpF, an E. coli aquaporin that facilitates the flow of glycerol, water and other small solutes, provides much insight into the molecular function and selectivity of aquaporins. Using GlpF and its atomic structure as a paradigm for the ten highly conserved human aquaporins, site-directed mutagenesis has been used to mutate residues that are possibly integral to the structure and function of different aquaporins. X-ray crystallography and other biophysical and molecular simulation methods allows for assessment of these changes at the structural and functional level. Initial attempts to convert the glycerol specific properties of GlpF towards a water specific aquaporin resulted in the shifting of GlpF channel properties towards that of the water aquaporins. This result reveals the great possibility of emulating and deciphering the function of other aquaporins with GlpF via mutagenesis and investigation of structure and function.
大肠杆菌水通道蛋白GlpF可促进甘油、水及其他小分子溶质的流动，其分辨率为2.2 Å的晶体结构为深入了解水通道蛋白的分子功能和选择性提供了诸多信息。以GlpF及其原子结构作为十种高度保守的人类水通道蛋白的范例，人们利用定点诱变技术对不同水通道蛋白结构和功能可能不可或缺的残基进行突变。X射线晶体学以及其他生物物理和分子模拟方法可在结构和功能层面评估这些变化。最初尝试将GlpF对甘油的特异性转变为对水的特异性水通道蛋白，结果导致GlpF通道特性向水通道蛋白的特性转变。这一结果揭示了通过诱变以及结构和功能研究，利用GlpF模拟和解读其他水通道蛋白功能的巨大可能性。
