User:Sean Callahan/Sandbox 1: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 8: | Line 8: | ||
==Structure== | ==Structure== | ||
LSD1 is found in ''Homo sapiens'' and its crystal structure was obtained in the presence of | LSD1 is found in ''Homo sapiens'' and its crystal structure was obtained in the presence of the FAD cofactor. LSD1, when compared to other histone binding proteins, contains both conserved and novel structural features. Its substrates are mono- or di-methylated lysine residues and its products are demethylated or mono-methylated lysine residues, respectively. | ||
===N-Terminus=== | ===N-Terminus=== | ||
Going in order of primary structure, the first 166 residues are believed to be unstructured and contain a nuclear localization signal. This area of the protein has also been shown to be susceptible to proteolytic cleavage, which may be to remove the localization signal and render protein inactive<ref name="Stavropoulos">PMID: 16799558</ref>. However, a mutant of LSD1, which contains residues 166-852 (essentially eliminating the unstructured region) has been shown to be stable and viable when compared to wild-type LSD1 in a photometric activity assay<ref name="Stavropoulos">PMID: 16799558</ref>. Unfortunately, this portion of the protein was unable to be crystallized<ref name="Stavropoulos">PMID: 16799558</ref>. | Going in order of primary structure, the first 166 residues are believed to be unstructured and contain a nuclear localization signal. This area of the protein has also been shown to be susceptible to proteolytic cleavage, which may be to remove the localization signal and render protein inactive<ref name="Stavropoulos">PMID: 16799558</ref>. However, a mutant of LSD1, which contains residues 166-852 (essentially eliminating the unstructured region) has been shown to be stable and viable when compared to wild-type LSD1 in a photometric activity assay<ref name="Stavropoulos">PMID: 16799558</ref>. Unfortunately, this portion of the protein was unable to be crystallized<ref name="Stavropoulos">PMID: 16799558</ref>. | ||
| Line 18: | Line 18: | ||
The interactions between the SWIRM and Oxidase domains create a <scene name='81/811711/Swirm-oxidase_interface/1'>cleft</scene> through a number of hydrophobic (van der Waals) interactions. The interior ends of the helices in the SWIRM domain contribute to the cleft, as well as the alpha helices from the oxidase domains. Because of its vicinity to the active site and FAD co-factor, it is believed that this cleft may serve as a site for additional histone tail binding<ref name="Stavropoulos">PMID: 16799558</ref>. | The interactions between the SWIRM and Oxidase domains create a <scene name='81/811711/Swirm-oxidase_interface/1'>cleft</scene> through a number of hydrophobic (van der Waals) interactions. The interior ends of the helices in the SWIRM domain contribute to the cleft, as well as the alpha helices from the oxidase domains. Because of its vicinity to the active site and FAD co-factor, it is believed that this cleft may serve as a site for additional histone tail binding<ref name="Stavropoulos">PMID: 16799558</ref>. | ||
===Tower Domain=== | ===Tower Domain=== | ||
A unique and defining feature of LSD1 is the 100 residue long insertion between the two parts of the oxidase domain in the primary structure. This <scene name='81/811711/Tower_domain/2'>Tower Domain</scene> spans from residues 419-520. This domain is unique, yet vital to LSD1 function. Specifically, it is hypothesized to be a binding platform of LSD1 to the [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048046/ CoREST complex] , as well as a site of allosteric regulation. The CoREST complex is a group of proteins responsible for the silencing of neuronal genes in non-neural cells, and the binding of LSD1 to this complex activates its demethylase activity. It is composed to two long alpha helices(TαA and TαB) that extend from the core of the protein. The helices hold each other in place through hydrophobic interactions. The TαB helix is the shorter of the two and is connected to a helix in the oxidase domain (αD). αD is essential for active site formation, and TαB is thought to be responsible for the correct <scene name='81/811711/Tab_and_ad_helix_interaction/1'>positioning</scene> of | A unique and defining feature of LSD1 is the 100 residue long insertion between the two parts of the oxidase domain in the primary structure. This <scene name='81/811711/Tower_domain/2'>Tower Domain</scene> spans from residues 419-520. This domain is unique, yet vital to LSD1 function. Specifically, it is hypothesized to be a binding platform of LSD1 to the [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048046/ CoREST complex] , as well as a site of allosteric regulation. The CoREST complex is a group of proteins responsible for the silencing of neuronal genes in non-neural cells, and the binding of LSD1 to this complex activates its demethylase activity. It is composed to two long alpha helices(TαA and TαB) that extend from the core of the protein. The helices hold each other in place through hydrophobic interactions. The TαB helix is the shorter of the two and is connected to a helix in the oxidase domain (αD). αD is essential for active site formation, and TαB is thought to be responsible for the correct <scene name='81/811711/Tab_and_ad_helix_interaction/1'>positioning</scene> of αD<ref name="Stavropoulos">PMID: 16799558</ref>. | ||
==Regulation== | ==Regulation== | ||
