High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR.
The three-dimensional structure of a member of the beta subfamily of chemokines, human macrophage inflammatory protein-1 beta (hMIP-1 beta), has been determined with the use of solution multidimensional heteronuclear magnetic resonance spectroscopy. Human MIP-1 beta is a symmetric homodimer with a relative molecular mass of approximately 16 kilodaltons. The structure of the hMIP-1 beta monomer is similar to that of the related alpha chemokine interleukin-8 (IL-8). However, the quaternary structures of the two proteins are entirely distinct, and the dimer interface is formed by a completely different set of residues. Whereas the IL-8 dimer is globular, the hMIP-1 beta dimer is elongated and cylindrical. This provides a rational explanation for the absence of cross-binding and reactivity between the alpha and beta chemokine subfamilies. Calculation of the solvation free energies of dimerization suggests that the formation and stabilization of the two different types of dimers arise from the burial of hydrophobic residues.
Lodi
P J
PJ
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Garrett
D S
DS
Kuszewski
J
J
Tsang
M L
ML
Weatherbee
J A
JA
Leonard
W J
WJ
Gronenborn
A M
AM
Clore
G M
GM
D000595:Amino Acid Sequence; D054407:Chemokine CCL4; D003196:Computer Graphics; D016207:Cytokines / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D016209:Interleukin-8 / Q000737:chemistry; D019402:Macrophage Inflammatory Proteins; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015846:Monokines / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
D054407:Chemokine CCL4; D016207:Cytokines; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D015846:Monokines