Huan He/Sandbox1
From Proteopedia
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'''THREE-DIMENSIONAL STRUCTURE OF IL-1β''' | '''THREE-DIMENSIONAL STRUCTURE OF IL-1β''' | ||
| - | The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues. | + | Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues. |
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[http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane. | [http://en.wikipedia.org/wiki/Interleukin-1_receptor Interleukin-1 receptor] complex with ligand and go through the plasma membrane. | ||
| - | <scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has | + | <scene name='57/571319/Scene_2/2'> Type 1 Interleukin-1 receptor complex with Interleukin-1 beta</scene> 3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The <scene name='57/571319/Scene_2/3'>complex</scene> has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3] |
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Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs. | Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs. | ||
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==Clinical significance== | ==Clinical significance== | ||
| - | IL-1 cytokines family are over-expressed at tumor sites or inflammatory, thus they could be used as bio-markers to diagnose in advance. Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage. | + | IL-1 cytokines family are over-expressed at tumor sites or inflammatory, thus they could be used as bio-markers to diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4] |
==Reference== | ==Reference== | ||
| + | [1] | ||
| + | [2]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260502/ Biophys J. 1992 April; 62(1): 112–115. ] | ||
| + | [3] | ||
| + | [4] | ||
Revision as of 16:48, 6 December 2013
Contents |
Interleukin-1 beta(IL-1β)
|
IL-1β along with IL-1α is one of cytokines secreted from local inflammatory cells, are belong to IL-1 family. while the former is dominate and they have been distinguished by the cell with which they interact. IL-1β precursor need to be activated by protease (convertase or IL-1β converting enzyme) to form IL-1 active species. The active mature IL-1 mediates several components of the acute phase reaction, including the febrile response, secretion of adrenocorticotropic hormone (ACIH), and the synthesis of acute phase proteins. interleukin 1(IL-1) cytokines could mediate innate and adaptive immunity[1].
Human Interleukin-1 Beta
THREE-DIMENSIONAL STRUCTURE OF IL-1β
Quoted from[2]:The molecule resembles a conical barrel with a shallow open face on one end and a closed face on the other. The molecule contains 12 antiparallel 13-strands, where six of these (131, 14, 15, 18, 19, and 1312) constitute an antiparallel 1 barrel. The overall structure of the molecule consists of three similar fragments (Fl, F2, F3), each containing two pairs of 1 strands. Three pairs of 1 strands (one pair from each of the fragments) form the six stranded barrel; the other three pairs cover one end of the barrel, referred to as the "closed end." The amino and carboxy termini are close to each other at the "open end" of the barrel. The molecule has internal pseudo threefold symmetry, with each subunit (Fl, F2, F3) having a 13L13 motif. There are five 1-hairpins in this molecule, two of them in the open end and three at the closed end. 24 hydrophobic side chains line the inner surface of the barrel and both the ends of the barrel have concentrations of exposed polar residues.
are present in the 3D structure. In the picture we could see was colored as purple and was colored as blue, respectively. Most ,which is dark red color, was buried inside of the protein.
TYPE-1 INTERLEUKIN-1 RECEPTOR COMPLEXED WITH INTERLEUKIN-1 BETA
Interleukin-1 receptor complex with ligand and go through the plasma membrane.
3D structure is showing here. Ribbon diagram of s-IL 1R complex to IL-1β. The has approximate dimensions of 97Å×52 Å ×35 Å with one s-IL1R molecule wrapping around the IL-1β molecule with 1:1 ratio. Quoted here： Domain 3 provides a 'lid' which covers most of the top of the IL-1β β-barrel, whereas domains 1 and 2 from a groove which binds to the lower rim of the barrel. Here,Domains 1,2 and 3 of s-IL 1R are colored light, medium and dark blue, respectively. IL-1β is yellow, with site A residues in green and site B residues in red.The structure is oriented so that the carboxy terminus of s-IL 1R and the cell membrane are at the bottom of the picture.[3]
Since IL-1α, IL-1β and IL-1ra all have the ability to bind to the type 1 IL-1 receptor(IL-1R), and the binding of IL-1α or IL-1β to IL-1R is an early step in IL-1 signal transduction, blocking this interaction may therefore be a useful target for the development of new drugs.
STRUCTURE OF THE INTERLEUKIN-1BETA SIGNALING COMPLEX
showed that the interface was most hydrogen-bonded and signal was transferred through the highly packed hydrophobic region between receptor accessory and IL-1R liganded with IL-1β . From the scenario, we
Clinical significance
IL-1 cytokines family are over-expressed at tumor sites or inflammatory, thus they could be used as bio-markers to diagnose in advance. Quoted here： Also recent studies have implicated IL-1 as an autocrine growth factor in certain acute and chronic myelocytic leukemias. The molecular cloning of a protease that generates active IL-1β provides new insight into IL-1 biology and offers a new target for the development of therapeutic agents. Also IL-1β receptor linker could be using as targeting binding site for therapeutic usage.[4]
Reference
[1] [2]B Veerapandian,Structure and function of interleukin-1, based on crystallographic and modeling studies,Biophys J. 1992 April; 62(1): 112–115. [3] [4]
