1tvx
From Proteopedia
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==Overview== | ==Overview== | ||
| - | alpha-Chemokines comprise a family of cytokines that are chemotactic for | + | alpha-Chemokines comprise a family of cytokines that are chemotactic for neutrophils and have a structure similar to platelet factor 4 (PF4), in which the first two cysteine residues are separated by one residue (Cys-X-Cys). The two alpha-chemokines, connective tissue activating peptide-III (CTAP-III) and neutrophil activating peptide-2 (NAP-2), are carboxyl-terminal fragments of platelet basic protein (PBP) that are generated by monocyte-derived proteases. NAP-2 strongly stimulates neutrophils that are present during inflammation whereas its precursors, PBP and CTAP-III, are inactive, although they also possess the highly conserved, amino-terminal sequence, Glu-Leu-Arg (ELR), that is critical for receptor binding. To resolve this conundrum, we have determined the crystal structure of recombinant Asp-CTAP, which has ten fewer amino-terminal residues than CTAP-III but five more than NAP-2. The space group is P2(1)with unit cell dimensions a = 43.8 A, b = 76.8 A, c = 43.8 A, and beta =97.0 degrees, and a tetramer in the asymmetric unit. The molecular replacement method, with the NAP-2 tetramer as a starting model, was used to determine the initial phase information. The final R-factor is 0.196 (Rfree = 0.251) for 2sigma data from 7.0 to 1.75 A resolution. This high-resolution model of Asp-CTAP is the longest defined structure of an alpha-chemokine to date. The electron density map shows an over-all structure for Asp-CTAP that is very similar to that of NAP-2, but with the additional five amino-terminal residues folding back through a type-II turn, thereby stabilizing the oligomeric "inactive" state, and masking the critical ELR receptor binding region that is exposed in the structure of NAP-2. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Edwards, B | + | [[Category: Edwards, B F.P.]] |
| - | [[Category: Malkowski, M | + | [[Category: Malkowski, M G.]] |
[[Category: cytokine]] | [[Category: cytokine]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:17:54 2008'' |
Revision as of 13:17, 21 February 2008
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NEUTROPHIL ACTIVATING PEPTIDE-2 VARIANT FORM M6L WITH FIVE ADDITIONAL AMINO TERMINAL RESIDUES (DSDLY)
Overview
alpha-Chemokines comprise a family of cytokines that are chemotactic for neutrophils and have a structure similar to platelet factor 4 (PF4), in which the first two cysteine residues are separated by one residue (Cys-X-Cys). The two alpha-chemokines, connective tissue activating peptide-III (CTAP-III) and neutrophil activating peptide-2 (NAP-2), are carboxyl-terminal fragments of platelet basic protein (PBP) that are generated by monocyte-derived proteases. NAP-2 strongly stimulates neutrophils that are present during inflammation whereas its precursors, PBP and CTAP-III, are inactive, although they also possess the highly conserved, amino-terminal sequence, Glu-Leu-Arg (ELR), that is critical for receptor binding. To resolve this conundrum, we have determined the crystal structure of recombinant Asp-CTAP, which has ten fewer amino-terminal residues than CTAP-III but five more than NAP-2. The space group is P2(1)with unit cell dimensions a = 43.8 A, b = 76.8 A, c = 43.8 A, and beta =97.0 degrees, and a tetramer in the asymmetric unit. The molecular replacement method, with the NAP-2 tetramer as a starting model, was used to determine the initial phase information. The final R-factor is 0.196 (Rfree = 0.251) for 2sigma data from 7.0 to 1.75 A resolution. This high-resolution model of Asp-CTAP is the longest defined structure of an alpha-chemokine to date. The electron density map shows an over-all structure for Asp-CTAP that is very similar to that of NAP-2, but with the additional five amino-terminal residues folding back through a type-II turn, thereby stabilizing the oligomeric "inactive" state, and masking the critical ELR receptor binding region that is exposed in the structure of NAP-2.
About this Structure
1TVX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The amino-terminal residues in the crystal structure of connective tissue activating peptide-III (des10) block the ELR chemotactic sequence., Malkowski MG, Lazar JB, Johnson PH, Edwards BF, J Mol Biol. 1997 Feb 21;266(2):367-80. PMID:9047370
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