Anion exchange protein 2 (AE2) is a
membrane transport protein
A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral membrane proteins, integral transmembr ...
that in humans is encoded by the ''SLC4A2''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
AE2 is functionally similar to the
Band 3
Band 3 anion transport protein, also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1), is a protein that is encoded by the gene in humans.
Band 3 anion transport protein is a phylogenetically-preserved ...
Cl−/
HCO3− exchange
Exchange or exchanged may refer to:
Arts, entertainment and media Film and television
* Exchange (film), or ''Deep Trap'', 2015 South Korean psychological thriller
* Exchanged (film), 2019 Peruvian fantasy comedy
* Exchange (TV program), 2021 Sou ...
protein.
Mice
A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
have been used to explore the function of AE2. AE2 contributes to
basolateral membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extra ...
HCO
3− transport in the
gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
.
AE2 is required for
spermiogenesis
Spermiogenesis is the final stage of spermatogenesis, during which the spermatids develop into mature spermatozoon, spermatozoa. At the beginning of the stage, the spermatid is a more or less circular cell containing a cell nucleus, nucleus, Golg ...
in mice.
AE2 is required for normal
osteoclast
An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...
function.
The activity of AE2 is sensitive to
pH.
AE3 has been suggested as a target for prevention of
diabetic vasculopathy.
Structure
The
cryo electron microscopic studies revealed that human AE2 protein forms a
homodimer
In biochemistry, a protein dimer is a macromolecular complex or protein multimer, multimer formed by two protein monomers, or single proteins, which are usually Non-covalent interaction, non-covalently bound. Many macromolecules, such as proteins ...
and stays in resting state of inward-facing conformation at physiological pH. A loop between transmembrane (TM) helices 10 and 11 extends from TM domain into its cytoplamic domain, forming a "trigger" locking the TM helices in the resting state. In addition, the C-terminal loop (CTD loop) inserts into the anion binding pocket to further block its activities.
Mechanism of ion exchange
During the process of acid secretion, the cellular pH increases, triggering the release of the "trigger" loop from the cytoplasmic domain.
This allows for the re-arrangement of the TM helices, while the CTD loop is forced out, enabling binding. Further conformational changes then turn the AE2 protein into an outward-facing conformation, releasing into the extracellular environment and capturing into the binding pocket. Finally, the AE2 protein returns to its inward-facing conformation and releases into the cytosol. This working cycle of the AE2 protein replaces a weak acid anion with a strong acid anion, thereby lowering the cellular pH and re-balancing pH homeostasis.
See also
*
Solute carrier family
The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO ...
References
Further reading
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Solute carrier family