1ESR

CRYSTAL STRUCTURE OF HUMAN MONOCYTE CHEMOTACTIC PROTEIN-2

Summary for 1ESR

• Entry DOI: 10.2210/pdb1esr/pdb
• Related: 1BO0 1DOK 1DOL 1DOM
• Descriptor: MONOCYTE CHEMOTACTIC PROTEIN 2 (2 entities in total)
• Functional Keywords: cytokine, chemokine, monocyte chemoattractant protein, hiv-1, pyroglutamic acid
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 8911.38

Authors

Blaszczyk, J.,Ji, X. (deposition date: 2000-04-10, release date: 2000-12-06, Last modification date: 2024-11-20)

Primary citation

Blaszczyk, J.,Coillie, E.V.,Proost, P.,Damme, J.V.,Opdenakker, G.,Bujacz, G.D.,Wang, J.M.,Ji, X.
Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors.
Biochemistry, 39:14075-14081, 2000

PubMed Abstract: 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.

PubMed: 11087354
DOI: 10.1021/bi0009340

Experimental method

X-RAY DIFFRACTION (2 Å)