2jyo
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(New page: 200px<br /><applet load="2jyo" size="350" color="white" frame="true" align="right" spinBox="true" caption="2jyo" /> '''NMR Solution structure of Human MIP-3alpha/C...)
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Revision as of 09:19, 23 January 2008
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NMR Solution structure of Human MIP-3alpha/CCL20
Overview
Human macrophage inflammatory protein-3alpha (MIP-3alpha), also known as, CCL20, is a 70 amino acid chemokine which exclusively binds to chemokine, receptor 6. In addition, the protein also has direct antimicrobial, antifungal, and antiviral activities. The solution structure of MIP-3alpha, was solved using two dimensional homonuclear proton NMR. The structure, reveals the characteristic chemokine fold with three antiparallel, beta-strands followed by a C-terminal alpha-helix. In contrast to the, crystal structures of MIP-3alpha, the solution structure was found to be, monomeric. Another difference between the NMR and crystal structures lies, in the angle of the alpha-helix with respect to the beta-strands, measuring 69 and approximately 56.5 degrees , respectively. NMR diffusion, and pH titration studies reveal a distinct tendency of MIP-3alpha to form, dimers at neutral pH and monomers at lower pH, dependent on the, protonation state of His 40. Molecular Dynamics simulations of both the, monomeric and dimeric forms of MIP-3alpha support the notion that the, chemokine undergoes a change in helix angle upon dimerization and also, highlight important hydrophobic and hydrogen bonding contacts made by His, 40 in the dimer interface. Moreover, a constrained N-terminus and a, smaller binding groove are observed in dimeric MIP-3alpha simulations, which could explain why monomeric MIP-3alpha may be more adept at receptor, binding and activation. The solution structure of a synthetic peptide, consisting of the last 20 residues of MIP-3alpha displays a highly, amphipathic alpha-helix, reminiscent of various antimicrobial peptides., Antimicrobial assays of this peptide reveal strong and moderate, bactericidal activities against Escherichia coli and Staphylococcus, aureus, respectively. This confirms that the C-terminal alpha-helical, region of MIP-3alpha plays a significant part in its broad anti-infective, activity.
About this Structure
2JYO is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Human Macrophage Inflammatory Protein-3{alpha}: Protein and Peptide NMR Solution Structures, Dimerization, Dynamics and Anti-Infective Properties., Chan DI, Hunter HN, Tack BF, Vogel HJ, Antimicrob Agents Chemother. 2007 Dec 17;. PMID:18086840
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