|
|
| (15 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:1s6w.gif|left|200px]]<br /><applet load="1s6w" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1s6w" /> | |
| - | '''Solution Structure of hybrid white striped bass hepcidin'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Solution Structure of hybrid white striped bass hepcidin== |
| - | Bass hepcidin was purified from the gill of hybrid striped bass (Morone, chrysops x Morone saxatilis) based on antimicrobial activity against, Escherichia coli. This 21-amino acid peptide has 8 cysteines engaged in 4, disulfide bonds and is very similar to human hepcidin, an antimicrobial, peptide with iron regulatory properties. To gain insight into potential, role(s) of bass hepcidin in innate immunity in fish, we synthesized the, peptide, characterized its antimicrobial activities in vitro, determined, its solution structure by NMR, and quantified hepatic gene expression in, vivo following infection of bass with the fish pathogens, Streptococcus, iniae or Aeromonas salmonicida. Its structure is very similar to that of, human hepcidin, including the presence of an antiparallel beta-sheet, a, conserved disulfide-bonding pattern, and a rare vicinal disulfide bond., Synthetic bass hepcidin was active in vitro against Gram-negative, pathogens and fungi but showed no activity against key Gram-positive, pathogens and a single yeast strain tested. Hepcidin was non-hemolytic at, microbicidal concentrations and had lower specific activity than, moronecidin, a broad spectrum, amphipathic, alpha-helical, antimicrobial, peptide constitutively expressed in bass gill tissue. Good synergism, between the bacterial killing activities of hepcidin and moronecidin was, observed in vitro. Hepcidin gene expression in bass liver increased, significantly within hours of infection with Gram-positive (S. iniae) or, Gram-negative (A. salmonicida) pathogens and was 4-5 orders of magnitude, above base-line 24-48 h post-infection. Our results suggest that hepcidin, plays a key role in the antimicrobial defenses of bass and that its, functions are potentially conserved between fish and human. | + | <StructureSection load='1s6w' size='340' side='right'caption='[[1s6w]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1s6w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Morone_chrysops_x_Morone_saxatilis Morone chrysops x Morone saxatilis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S6W FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1s6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s6w OCA], [https://pdbe.org/1s6w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s6w RCSB], [https://www.ebi.ac.uk/pdbsum/1s6w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s6w ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/HEPC_MORCS HEPC_MORCS] Seems to act as a signaling molecule involved in the maintenance of iron homeostasis. Seems to be required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages (By similarity). Antimicrobial activity against Gram-negative bacteria such as E.coli. |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Bass hepcidin was purified from the gill of hybrid striped bass (Morone chrysops x Morone saxatilis) based on antimicrobial activity against Escherichia coli. This 21-amino acid peptide has 8 cysteines engaged in 4 disulfide bonds and is very similar to human hepcidin, an antimicrobial peptide with iron regulatory properties. To gain insight into potential role(s) of bass hepcidin in innate immunity in fish, we synthesized the peptide, characterized its antimicrobial activities in vitro, determined its solution structure by NMR, and quantified hepatic gene expression in vivo following infection of bass with the fish pathogens, Streptococcus iniae or Aeromonas salmonicida. Its structure is very similar to that of human hepcidin, including the presence of an antiparallel beta-sheet, a conserved disulfide-bonding pattern, and a rare vicinal disulfide bond. Synthetic bass hepcidin was active in vitro against Gram-negative pathogens and fungi but showed no activity against key Gram-positive pathogens and a single yeast strain tested. Hepcidin was non-hemolytic at microbicidal concentrations and had lower specific activity than moronecidin, a broad spectrum, amphipathic, alpha-helical, antimicrobial peptide constitutively expressed in bass gill tissue. Good synergism between the bacterial killing activities of hepcidin and moronecidin was observed in vitro. Hepcidin gene expression in bass liver increased significantly within hours of infection with Gram-positive (S. iniae) or Gram-negative (A. salmonicida) pathogens and was 4-5 orders of magnitude above base-line 24-48 h post-infection. Our results suggest that hepcidin plays a key role in the antimicrobial defenses of bass and that its functions are potentially conserved between fish and human. |
| | | | |
| - | ==About this Structure==
| + | Bass hepcidin synthesis, solution structure, antimicrobial activities and synergism, and in vivo hepatic response to bacterial infections.,Lauth X, Babon JJ, Stannard JA, Singh S, Nizet V, Carlberg JM, Ostland VE, Pennington MW, Norton RS, Westerman ME J Biol Chem. 2005 Mar 11;280(10):9272-82. Epub 2004 Nov 16. PMID:15546886<ref>PMID:15546886</ref> |
| - | 1S6W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S6W OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | Bass hepcidin synthesis, solution structure, antimicrobial activities and synergism, and in vivo hepatic response to bacterial infections., Lauth X, Babon JJ, Stannard JA, Singh S, Nizet V, Carlberg JM, Ostland VE, Pennington MW, Norton RS, Westerman ME, J Biol Chem. 2005 Mar 11;280(10):9272-82. Epub 2004 Nov 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15546886 15546886]
| + | </div> |
| - | [[Category: Single protein]] | + | <div class="pdbe-citations 1s6w" style="background-color:#fffaf0;"></div> |
| - | [[Category: Babon, J.J.]] | + | == References == |
| - | [[Category: Norton, R.S.]] | + | <references/> |
| - | [[Category: Pennington, M.W.]] | + | __TOC__ |
| - | [[Category: Singh, S.]] | + | </StructureSection> |
| - | [[Category: Westerman, M.E.]] | + | [[Category: Large Structures]] |
| - | [[Category: two strand antiparalell beta sheet]]
| + | [[Category: Morone chrysops x Morone saxatilis]] |
| - | | + | [[Category: Babon JJ]] |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 02:09:32 2007''
| + | [[Category: Norton RS]] |
| | + | [[Category: Pennington MW]] |
| | + | [[Category: Singh S]] |
| | + | [[Category: Westerman ME]] |
| Structural highlights
Function
HEPC_MORCS Seems to act as a signaling molecule involved in the maintenance of iron homeostasis. Seems to be required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages (By similarity). Antimicrobial activity against Gram-negative bacteria such as E.coli.
Publication Abstract from PubMed
Bass hepcidin was purified from the gill of hybrid striped bass (Morone chrysops x Morone saxatilis) based on antimicrobial activity against Escherichia coli. This 21-amino acid peptide has 8 cysteines engaged in 4 disulfide bonds and is very similar to human hepcidin, an antimicrobial peptide with iron regulatory properties. To gain insight into potential role(s) of bass hepcidin in innate immunity in fish, we synthesized the peptide, characterized its antimicrobial activities in vitro, determined its solution structure by NMR, and quantified hepatic gene expression in vivo following infection of bass with the fish pathogens, Streptococcus iniae or Aeromonas salmonicida. Its structure is very similar to that of human hepcidin, including the presence of an antiparallel beta-sheet, a conserved disulfide-bonding pattern, and a rare vicinal disulfide bond. Synthetic bass hepcidin was active in vitro against Gram-negative pathogens and fungi but showed no activity against key Gram-positive pathogens and a single yeast strain tested. Hepcidin was non-hemolytic at microbicidal concentrations and had lower specific activity than moronecidin, a broad spectrum, amphipathic, alpha-helical, antimicrobial peptide constitutively expressed in bass gill tissue. Good synergism between the bacterial killing activities of hepcidin and moronecidin was observed in vitro. Hepcidin gene expression in bass liver increased significantly within hours of infection with Gram-positive (S. iniae) or Gram-negative (A. salmonicida) pathogens and was 4-5 orders of magnitude above base-line 24-48 h post-infection. Our results suggest that hepcidin plays a key role in the antimicrobial defenses of bass and that its functions are potentially conserved between fish and human.
Bass hepcidin synthesis, solution structure, antimicrobial activities and synergism, and in vivo hepatic response to bacterial infections.,Lauth X, Babon JJ, Stannard JA, Singh S, Nizet V, Carlberg JM, Ostland VE, Pennington MW, Norton RS, Westerman ME J Biol Chem. 2005 Mar 11;280(10):9272-82. Epub 2004 Nov 16. PMID:15546886[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lauth X, Babon JJ, Stannard JA, Singh S, Nizet V, Carlberg JM, Ostland VE, Pennington MW, Norton RS, Westerman ME. Bass hepcidin synthesis, solution structure, antimicrobial activities and synergism, and in vivo hepatic response to bacterial infections. J Biol Chem. 2005 Mar 11;280(10):9272-82. Epub 2004 Nov 16. PMID:15546886 doi:M411154200
|
