Newby Zachary E R, O'Connell Joseph, Robles-Colmenares Yaneth, Khademi Shahram, Miercke Larry J, Stroud Robert M
Department of Chemistry, Genentech Hall, School of Medicine, University of California in San Francisco, 600 16th Street, San Francisco, California 94158-2517, USA.
Nat Struct Mol Biol. 2008 Jun;15(6):619-25. doi: 10.1038/nsmb.1431. Epub 2008 May 25.
The 2.05-A resolution structure of the aquaglyceroporin from the malarial parasite Plasmodium falciparum (PfAQP), a protein important in the parasite's life cycle, has been solved. The structure provides key evidence for the basis of water versus glycerol selectivity in aquaporin family members. Unlike its closest homolog of known structure, GlpF, the channel conducts both glycerol and water at high rates, framing the question of what determines high water conductance in aquaporin channels. The universally conserved arginine in the selectivity filter is constrained by only two hydrogen bonds in GlpF, whereas there are three in all water-selective aquaporins and in PfAQP. The decreased cost of dehydrating the triply-satisfied arginine cation may provide the basis for high water conductance. The two Asn-Pro-Ala (NPA) regions of PfAQP, which bear rare substitutions to Asn-Leu-Ala (NLA) and Asn-Pro-Ser (NPS), participate in preserving the orientation of the selectivity filter asparagines in the center of the channel.
已解析出疟原虫恶性疟原虫（PfAQP）水甘油通道蛋白的2.05埃分辨率结构，该蛋白在疟原虫生命周期中具有重要作用。该结构为水通道蛋白家族成员中水与甘油选择性的基础提供了关键证据。与已知结构的最相近同源物GlpF不同，该通道能高效传导甘油和水，这引发了关于决定水通道蛋白通道高水导率因素的问题。选择性过滤器中普遍保守的精氨酸在GlpF中仅受两个氢键约束，而在所有水选择性水通道蛋白和PfAQP中则有三个氢键。三重满足的精氨酸阳离子脱水成本的降低可能为高水导率提供基础。PfAQP的两个天冬酰胺 - 脯氨酸 - 丙氨酸（NPA）区域罕见地替换为天冬酰胺 - 亮氨酸 - 丙氨酸（NLA）和天冬酰胺 - 脯氨酸 - 丝氨酸（NPS），它们参与维持通道中心选择性过滤器天冬酰胺的取向。
