User:KrystalMarquis/p11 Protein Project

Function
p11 protein is essential in the regulation of serotonin signaling in the brain. Serotonin, 5-hydroxytriptamine, is a neurotransmitter found in the central and peripheral nervous system. It is involved in mechanisms responsible for memory formation and learning but is most known for its role in the regulation muscle contraction, appetite, sleep, and mood. Varying levels of serotonin found in the brain are associated with the development of mood disorders, for instance depression. p11 interacts with the serotonin receptor proteins, 5-HT receptors such as 5-HT1B, modulating the receptor signal transduction pathways activated by the binding of serotonin. p11 also recruits the cell surface expression of 5-HT4, increasing its concentration at the synapse. As a result, serotonin-dependent activities occur more rapidly. 5-HT4 is involved in the regulation of kinase activity in the central nervous system, phosphorylating target proteins, and facilitating endosomal activities. p11 is coexpressed with 5-HT4 mRNA and its protein in parts of the brain associated with depression suggesting that their functions are linked and influence mood.

Low levels of p11 can be observed in the brain tissue of people diagnosed with depression. Mice displaying depression-like symptoms also exhibit lower concentrations of the p11 protein. Conversely, brain tissue of patients that did not suffer from depression presented with higher levels of the p11 protein. Furthermore, mice with adequate levels of the protein appeared to be treated with anti-depressant drugs.

Because of its ability to transport proteins related to serotonin signaling and its correlation with symptoms of mood disorders, p11 is a target for drug therapy.

Structure
p11 has dimeric and tetrameric conformations. The dimerized form of the protein is created a bond between the H1 and H4 helices. The four helices of p11 are found in an antiparallel arrangement with the hydrophobic regions creating a central pore.

p11 is classified as S-100 protein as it structure resembles that of the S-100A1 and S-100B. S-100 proteins are distinguished by a helix-loop-helix motif, also known as the "EF-hand"-type, that recognizes and binds calcium ions. S-100 proteins have been implicated in the regulation of cytoskeleton assembly, cytosolic enzymes and membrane dynamics. Its involvement with the cytoskeleton may aid p11 in the transport of other proteins through the cell and to the cell membrane. Unlike other S-100 proteins, mutations due to deletions and substitutions has rendered p11 incapable of binding calcium. A protein called annexin II binds to p11 at the Ca2+ binding site. Annxxin II has been implicated in membrane-cytoskeleton interactions, and regulating ion currents and substances across the membrane. p11 and annexin II form a heterotetrameric protein complex. This tetrameric complex is more stable than the p11 dimer, therefore the overexpression of the annexin II gene results in higher levels p11.