1tvx
From Proteopedia
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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
Page seeded by OCA on Fri Feb 15 16:58:41 2008
