Structure of human MIP-3alpha chemokine

Abstract

The structure of the human macrophage inflammatory protein-3alpha (MIP-3alpha) has been determined at 1.81 angstroms resolution by X-ray crystallography. The dimer crystallized in the tetragonal space group I4, with unit-cell parameters a = b = 83.99, c = 57.20 angstroms. The crystals exhibit two molecules in the asymmetric unit. The structure was solved by the molecular-replacement method and the model was refined to a conventional R value of 20.6% (R(free) = 25.7%). MIP-3alpha possesses the same monomeric structure as previously described for other chemokines. However, in addition to limited structural changes in the beta1-beta2 hairpin of monomer B, the electron density is fully defined for a few extra residues at the N- and C-termini of monomer A and the C-terminus of monomer B compared with MIP-3alpha in space group P6(1). As the N-terminal and loop regions have been shown to be critical for receptor binding and signaling, this additional structural information may help in determining the basis of the CCR6 selectivity of MIP-3alpha.

Figure 1

Superimposed C^α backbone structures of human MIPP61 in grey and MIPPI4 in black showing the long N- and C-termini of monomer A. The alternative orientation of the β-turn can also be seen in monomer B. The r.m.s. difference in Asp5–Lys65 C^α atomic positions, calculated with the LSQMAN option in O, is 0.85 Å (Jones et al., 1991 ▶). This figure was created using the program MOLMOL (Koradi et al., 1996 ▶).

Figure 2

Ribbon diagram of the overall three-dimensional structure of the dimer of human MIP-3α. The dimer is composed of a six-stranded β-sheet and two parallel α-helices. β-Strands are shown as arrows and α-helices as coils. This figure was generated with the program MOLMOL (Koradi et al., 1996 ▶).

Figure 3

Stick representation of the well defined N-terminal residues Ser2, Asn3 and Phe4 of monomer A that may play a role in the stabilization of the dimer.