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| | <StructureSection load='5i7j' size='340' side='right'caption='[[5i7j]], [[Resolution|resolution]] 2.54Å' scene=''> | | <StructureSection load='5i7j' size='340' side='right'caption='[[5i7j]], [[Resolution|resolution]] 2.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5i7j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I7J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I7J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5i7j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I7J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I7J FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5i7l|5i7l]], [[5i7k|5i7k]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.544Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BPIFA1, LUNX, NASG, PLUNC, SPLUNC1, SPURT, UNQ787/PRO1606 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5i7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i7j OCA], [https://pdbe.org/5i7j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i7j RCSB], [https://www.ebi.ac.uk/pdbsum/5i7j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i7j ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5i7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i7j OCA], [http://pdbe.org/5i7j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i7j RCSB], [http://www.ebi.ac.uk/pdbsum/5i7j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i7j ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BPIA1_HUMAN BPIA1_HUMAN]] May be involved in the airway inflammatory response after exposure to irritants. May be associated with tumor progression. May play a role in innate immune responses of the upper airways.<ref>PMID:11425234</ref> | + | [https://www.uniprot.org/uniprot/BPIA1_HUMAN BPIA1_HUMAN] May be involved in the airway inflammatory response after exposure to irritants. May be associated with tumor progression. May play a role in innate immune responses of the upper airways.<ref>PMID:11425234</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Redinbo, M R]] | + | [[Category: Redinbo MR]] |
| - | [[Category: Walton, W G]] | + | [[Category: Walton WG]] |
| - | [[Category: Antimicrobial protein]]
| + | |
| - | [[Category: Innate pulmonary defense protein]]
| + | |
| Structural highlights
Function
BPIA1_HUMAN May be involved in the airway inflammatory response after exposure to irritants. May be associated with tumor progression. May play a role in innate immune responses of the upper airways.[1]
Publication Abstract from PubMed
SPLUNC1 is an abundantly secreted innate immune protein in the mammalian respiratory tract that exerts bacteriostatic and antibiofilm effects, binds to lipopolysaccharide (LPS), and acts as a fluid-spreading surfactant. Here, we unravel the structural elements essential for the surfactant and antimicrobial functions of human SPLUNC1 (short palate lung nasal epithelial clone 1). A unique alpha-helix (alpha4) that extends from the body of SPLUNC1 is required for the bacteriostatic, surfactant, and LPS binding activities of this protein. Indeed, we find that mutation of just four leucine residues within this helical motif to alanine is sufficient to significantly inhibit the fluid spreading abilities of SPLUNC1, as well as its bacteriostatic actions against Gram-negative pathogens Burkholderia cenocepacia and Pseudomonas aeruginosa. Conformational flexibility in the body of SPLUNC1 is also involved in the bacteriostatic, surfactant, and LPS binding functions of the protein as revealed by disulfide mutants introduced into SPLUNC1. In addition, SPLUNC1 exerts antibiofilm effects against Gram-negative bacteria, although alpha4 is not involved in this activity. Interestingly, though, the introduction of surface electrostatic mutations away from alpha4 based on the unique dolphin SPLUNC1 sequence, and confirmed by crystal structure, is shown to impart antibiofilm activity against Staphylococcus aureus, the first SPLUNC1-dependent effect against a Gram-positive bacterium reported to date. Together, these data pinpoint SPLUNC1 structural motifs required for the antimicrobial and surfactant actions of this protective human protein.
Structural Features Essential to the Antimicrobial Functions of Human SPLUNC1.,Walton WG, Ahmad S, Little MS, Kim CS, Tyrrell J, Lin Q, Di YP, Tarran R, Redinbo MR Biochemistry. 2016 May 31;55(21):2979-91. doi: 10.1021/acs.biochem.6b00271. Epub , 2016 May 17. PMID:27145151[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lindahl M, Stahlbom B, Tagesson C. Identification of a new potential airway irritation marker, palate lung nasal epithelial clone protein, in human nasal lavage fluid with two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time of flight. Electrophoresis. 2001 May;22(9):1795-800. PMID:11425234 doi:<1795::AID-ELPS1795>3.0.CO;2-J 10.1002/1522-2683(200105)22:9<1795::AID-ELPS1795>3.0.CO;2-J
- ↑ Walton WG, Ahmad S, Little MS, Kim CS, Tyrrell J, Lin Q, Di YP, Tarran R, Redinbo MR. Structural Features Essential to the Antimicrobial Functions of Human SPLUNC1. Biochemistry. 2016 May 31;55(21):2979-91. doi: 10.1021/acs.biochem.6b00271. Epub , 2016 May 17. PMID:27145151 doi:http://dx.doi.org/10.1021/acs.biochem.6b00271
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