Crystal structure of human Band3 (anion exchanger)

人AE1是一种110 kDa的糖蛋白。它由两个结构域组成，一个是胞质N-末端结构域(残基1-360)，另一个是完整膜结构域(残基361-911)。阴离子交换是由C末端结构域催化的。然而，只有细胞质N-末端结构域的晶体结构被确定，该结构域作为其他蛋白质的锚定点，包括支架蛋白ankyrin和脱氧血红蛋白，已经被确定。因此，这种基本蛋白质的拓扑结构、底物识别和阴离子传输机制的细节仍不清楚。我们分析了人AE1膜结构域在3.4埃分辨率下的晶体结构，该结构域由一个共价结合的H_2DDS-抑制物与来自单抗的Fab片段形成的复合体锁定在外向开放构象中。我们还需要更高分辨率的内向开放构象或外向开放构象的结构来理解AE1的完全阴离子交换机制。

Human AE1 is a 110kDa glycoprotein. It is built from two domains, a cytosolic N-terminal domain (residues 1-360) and an integral membrane domain (residues 361-911). Anion exchange is catalysed by the C-terminal domain. However, only the crystal structure of the cytosolic N-terminal domain, important as an anchoring point for other proteins including the scaffolding protein ankyrin and deoxy-hemoglobin, has been determined. As such the details of the topology, the substrate recognition, and the anion-transport mechanism of this fundamental protein remain unclear. We analyzed the crystal structure at 3.4 angstrom resolution of the membrane domain of human AE1 locked in an outward open conformation by a covalently bound H2DIDS-inhibitor in complex with a Fab fragment from a monoclonal antibody. We also need the structure of an inward-facing open conformation or an outward-facing open conformation at higher resolution to understand the fully anion exchange mechanism of AE1.