1esr
CRYSTAL STRUCTURE OF HUMAN MONOCYTE CHEMOTACTIC PROTEIN-2
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OverviewOverview
Monocyte chemotactic protein 2 (MCP-2) is a CC chemokine that utilizes, multiple cellular receptors to attract and activate human leukocytes., MCP-2 is a potent inhibitor of HIV-1 by virtue of its high-affinity, binding to the receptor CCR5, one of the major coreceptors for HIV-1., Although a few structures of CC chemokines have been reported, none of, these was determined with the N-terminal pyroglutamic acid residue (pGlu1), and a complete C-terminus. pGlu1 is essential for the chemotactic activity, of MCP-2. Recombinant MCP-2 has Gln1 at the N terminus, 12-15% of which, cyclizes automatically and forms pGlu1. The chemotactic activity of such, MCP-2 mixture, which contains 12-15% pGlu1-form and 85-88% Gln1-form, protein, is approximately 10 times lower when compared with that of fully, cyclized MCP-2 preparation. Therefore, this chemokine is practically, inactive without pGlu1. We have determined the complete crystal structure, of MCP-2 that contains both pGlu1 and an intact C-terminus. With the, existence of pGlu1, the conformation of the N-terminus allows two, additional interactions between the two subunits of MCP-2 dimer: a, hydrogen bond between pGlu1 and Asn17 and a salt bridge between Asp3 and, Arg18. Consequently, both pGlu1 are anchored and buried, and thereby, both, N-terminal regions are protected against protease degradation. We have, also observed not previously reported extended helical nature of the C, terminal region, which covers residues 58-74.
About this StructureAbout this Structure
1ESR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors., Blaszczyk J, Coillie EV, Proost P, Damme JV, Opdenakker G, Bujacz GD, Wang JM, Ji X, Biochemistry. 2000 Nov 21;39(46):14075-81. PMID:11087354
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