As well as being expressed in the kidney, AE1 is the most abundant protein in the membrane of red blood cells, or erythrocytes, and helps prevent tissue damage by regulating oxygen supply.
Carbon dioxide, produced when food is burnt for energy, is released into the bloodstream and, on encountering erythrocytes, is converted into bicarbonate (HCO3¯) by the enzyme carbonic anhydrase bound to AE1. In a crucial step—the ‘chloride shift’—chloride is exchanged for HCO3¯ across the erythrocyte membrane via AE1. This lowers erythrocyte pH, resulting in the regulated release of oxygen from hemoglobin.
Despite its importance, there is limited structural information about AE1, particularly the membrane-spanning domain. “Like many membrane proteins, AE1 is very fragile, making structural information difficult to obtain,” says Hirai.
Naotaka Hamasaki and colleagues at Nagasaki International University and Kyushu University purified AE1 stably with the membrane domain fixed in an outward-open conformation, and good two-dimensional crystals were prepared at RIKEN by Tomohiro Yamaguchi. “These were critical steps for structural analysis,” explains Hirai.
The researchers merged 31 images, each taken from a different angle, to produce a three-dimensional image. Interestingly, they found structural similarities between AE1 and a bacterial transporter protein related to a class of chloride channels called ‘ClC channels’ found in animals, including humans.
DNA sequence information is available for the anion exchanger and ClC gene families, but the researchers are the first to uncover structural similarities between the encoded proteins.
ClC channels of mammals conduct chloride ions and are involved in regulating the electrical excitation of skeletal muscles. The bacterial protein, however, functions as a transporter, exchanging chloride ions and protons across the bacterial membrane.
“AE1 has a putative chloride binding site similar to that of the bacterial ClC protein, although this is yet to be proven biochemically,” explains Hirai.
The observed resemblance between AE1 and ClC should help address the chloride transport mechanism, which is not well understood for either family.
“We need to improve the resolution of the current outward-open conformation structure of AE1 and solve the structure of the inward-open conformation to understand the conformational change during transport,” Hirai notes.
AE1 mutations are associated with the human genetic disorders Southeast Asian ovalocytosis and distal renal tubular acidosis, so structural knowledge of AE1 might eventually lead to treatments.
The corresponding author for this highlight is based at the Three-dimensional Microscopy Research Team, RIKEN SPring-8 Center
1. Yamaguchi, T., Ikeda, Y., Abe, Y., Kuma, H., Kang, D., Hamasaki, N. & Hirai, T. Structure of the membrane domain of human erythrocyte anion exchanger 1 revealed by electron crystallography. Journal of Molecular Biology 397, 179–189 (2010).
| Research asia research news
Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo
Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
23.05.2018 | Life Sciences
23.05.2018 | Life Sciences
23.05.2018 | Physics and Astronomy