1A7M

LEUKAEMIA INHIBITORY FACTOR CHIMERA (MH35-LIF), NMR, 20 STRUCTURES

Summary for 1A7M

• Entry DOI: 10.2210/pdb1a7m/pdb
• Descriptor: LEUKEMIA INHIBITORY FACTOR (1 entity in total)
• Functional Keywords: cytokine, four helical bundle
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 19822.94

Authors

Hinds, M.G.,Maurer, T.,Zhang, J.-G.,Nicola, N.A.,Norton, R.S. (deposition date: 1998-03-16, release date: 1999-04-20, Last modification date: 2024-10-16)

Primary citation

Hinds, M.G.,Maurer, T.,Zhang, J.G.,Nicola, N.A.,Norton, R.S.
Solution structure of leukemia inhibitory factor.
J.Biol.Chem., 273:13738-13745, 1998

PubMed Abstract: The solution structure of a murine-human chimera of leukemia inhibitory factor (LIF), a 180-residue cytokine with a molecular mass of 20 kDa, has been determined using multidimensional heteronuclear NMR techniques. The protein contains four alpha-helices, the relative orientations of which are well defined on the basis of long-range interhelical nuclear Overhauser effects. The helices are arranged in an up-up-down-down orientation, as found in other four-helix bundle cytokines, and the overall topology of the chimera is similar to that of the crystal structure of murine LIF (Robinson, R. C., Grey, L. M., Staunton, D., Vankelecom, H. Vernallis, A. B., Moreau, J. F., Stuart, D. I., Heath, J. K., and Jones, E. Y. (1994) Cell 77, 1101-1116). Differences between the structures are evident in the N-terminal region, where the peptide bond preceding Pro17 has a trans-conformation in solution but a cis-conformation in the crystal, and in the small antiparallel beta-sheet encompassing residues in the N terminus and the CD loop in the crystal structure, which is not apparent in solution. There are also minor differences in the extent of the helices. Other than at the N terminus, the main difference between the two structures occurs at the C-terminal end of the CD loop. As this loop is close to a receptor-binding site on LIF that makes a major contribution to high affinity binding to the LIF receptor alpha-chain, these differences between the solution and crystal structures should be taken into account in structural models of LIF receptor interactions.

PubMed: 9593715
DOI: 10.1074/jbc.273.22.13738

Experimental method

SOLUTION NMR