Department of Applied Sciences, University Parthenope of Naples, Centro Direzionale Isola C4, Naples I-80143, Italy.
Protein Sci. 2013 Apr;22(4):455-66. doi: 10.1002/pro.2227. Epub 2013 Feb 26.
AQP11 and AQP12 are the most distantly related paralogs of the aquaporin family in human. They share indeed a low sequence similarity with other aquaporins and exhibit a modified N-terminal NPA signature motif. Furthermore, they have an anomalous subcellular localization. The AQP11 and AQP12 biological role remains to be fully clarified and their ability to allow transport of water is still debated. We have built accurate 3D-models for AQP11 and AQP12 and comprehensively compared their sequence and structure to other known aquaporins. In order to investigate whether they appear compatible or not with water permeability, we especially focused on the amino acid composition and electrostatics of their channels, keeping the structure of the low-water efficiency AQP0 as a reference system. Our analysis points out a possible alternative ar/R site and shows that these aquaporins feature unique residues at key pore-lining positions that make the shape, composition and electrostatics of their channel peculiar. Such residues can represent pivotal hints to study and explain the AQP11 and AQP12 biological and molecular function.
水通道蛋白 11（AQP11）和水通道蛋白 12（AQP12）是人类水通道蛋白家族中亲缘关系最远的两个旁系同源物。它们与其他水通道蛋白确实具有较低的序列相似性，并且表现出修饰的 N 端 NPA 特征基序。此外，它们具有异常的亚细胞定位。AQP11 和 AQP12 的生物学作用仍有待充分阐明，它们允许水运输的能力仍存在争议。我们为 AQP11 和 AQP12 构建了精确的 3D 模型，并全面比较了它们的序列和结构与其他已知水通道蛋白的差异。为了研究它们是否与水通透性相容，我们特别关注了它们通道的氨基酸组成和静电特性，同时以低水效率 AQP0 的结构作为参考系统。我们的分析指出了一个可能的替代 ar/R 位点，并表明这些水通道蛋白在关键孔道衬里位置具有独特的残基，使它们的通道形状、组成和静电特性具有独特性。这些残基可以为研究和解释 AQP11 和 AQP12 的生物学和分子功能提供重要线索。
