Novel Fold and Putative Receptor Binding Site of Granulocyte-Macrophage Colony-Stimulating Factor

Diederichs, Kay; Boone, T.; Karplus, P.A.

doi:10.1126/science.1837174

Cited by 202 publications

(122 citation statements)

References 31 publications

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“…The structure of human growth hormone (HGH) was determined in a complex with the soluble part of its receptor (HGH-R). All of the cytokines listed above belong to the class of four-helix bundles with up-up-downdown topology, and structural similarities between them were noted previously (Diederichs et al, 1991 ;de Vos et al, 1992;Pandit et al, 1992;Wlodawer et al, 1992).…”

supporting

confidence: 53%

“…4; Kinemage 3). The participation of the end of helix D in receptor binding was reported for IL-4 (Postlethwaite & Seyer, 1991; Kruse et al, 1992), IL-2 (Zurawski & Zurawski, 1988;Zurawski et al, 1990), and GM-CSF (Diederichs et al, 1991;Shanafelt et al, 1991;Walter et al, 1992a). Positive charge is conserved at positions 115 and 117 (IL-4 numbering) in IL-2 and GM-CSF, respectively, and positively charged residues are found in HGH in positions structurally equivalent to residues 121 and 126 in IL-4, but nevertheless this patch appears to be a particular feature of IL-4.…”

Section: Helix Dmentioning

confidence: 79%

“…For IL-4 and GM-CSF, this alignment is identical to that of Bazan (1992), which was based on an X-ray model of GM-CSF (Diederichs et al, 1991) and on an NMR model of IL-4 (Smith et al, 1992). However, our alignment of 1L-2 with the other two hematopoietins is not the same as that determined by Bazan (1992).…”

Section: Sequence Alignmentmentioning

confidence: 90%

“…The coordinate sets used directly in all comparisons described here include the X-ray structures of IL-4 refined in our laboratory to R = 0.218 at 2.25 A resolution (Wlodawer et al, 1992), GM-CSF refined to R = 0.205 at 2.4 A (Diederichs et al, 1991), and IL-2 refined at 2.5 A to R = 0.202 (McKay, 1992). The IL-4 model included all 129 residues found in the protein sequence, GM-CSF included 119 out of 127 residues (arbitrarily, only molecule 1 was considered in comparisons), and the model of IL-2 included 121 out of 133 residues (again only molecule 1 was used).…”

Section: Methodsmentioning

confidence: 99%

“…Medium-to high-resolution structures of several of the hematopoietins have now been determined by X-ray crystallography and NMR. These include GM-CSF (Diederichs et al, 1991;Walter et al, 1992a), macrophage colony-stimulating factor (Pandit et al, 1992), granulocyte colony-stimulating factor (Hill et al, 1993), IL-5 (Milburn et al, 1993), the recently corrected structure of IL-2 (Brandhuber et al, 1987;McKay, 1992), and the crystal and NMR structures of IL-4, determined independently in four different laboratories (Powers et al, 1992;Smith et al, 1992; 1992b; Wlodawer et al, 1992). Structures of other molecules with similar folds, for example, porcine (AbdelMeguid et al, 1987) and human (de Vos et al, 1992) growth hormones, were also determined crystallographically.…”

mentioning

confidence: 99%

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Hematopoietic cytokines: Similarities and differences in the structures, with implications for receptor binding

1993

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Crystal and NMR structures of helical cytokines-interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-2 (IL-2)-have been compared. Root mean square deviations in the C, coordinates for the conserved regions of the helices were 1-2 A between different cytokines, about twice the differences observed for independently determined crystal and solution structures of IL-4. Considerable similarity in amino acid sequence in the areas expected to interact with the receptors was detected, and the available mutagenesis data for these cytokines were correlated with structure conservation. Models of cytokine-receptor interactions were postulated for IL-4 based on its structure as well as on the published structure of human growth hormone interacting with its receptors (de Vos, A.M., Ultsch, M., & Kossiakoff, A.A., 1992, Science 255, 306-312). Patches of positively charged residues on the surfaces of helices C and D of IL-4 may be responsible for the interactions with the negatively charged residues found in the complementary parts of the IL-4 receptors.

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supporting

confidence: 53%

Section: Helix Dmentioning

confidence: 79%

Section: Sequence Alignmentmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Hematopoietic cytokines: Similarities and differences in the structures, with implications for receptor binding

1993

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Computational simulations of stem-cell factor/c-Kit receptor interaction

1996

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Stem-cell factor (SCF) is a noncovalent homodimeric cytokine that exhibits profound biological function in the early stages of hematopoiesis by binding to a cell surface tyrosine kinase receptor that is encoded by the c-Kit proto-oncogene. The results obtained from a combined implementation of homology-based molecular modeling and computational simulations in the study of species-specific SCF/ c-Kit interactions are reported. The structural models of the human and rat SCF ligands are based on the close structural similarity to the cytokine M-CSF, whose C alpha structure has recently become available. The constant domains of the human Fc fragment are used as a template for the ligand binding domains of the c-Kit receptor. The factors responsible for the stabilization of the SCF quaternary structure and the molecular determinants for ligand recognition and ligand specificity have been identified by assessing the conformational, topographical, and dynamic features of the isolated ligands and of the ligand-receptor complexes.

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Refined crystal structure and mutagenesis of human granulocyte-macrophage colony-stimulating factor

et al. 1996

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The crystal structure of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) has been refined against data extending to a resolution of -2.4 A along a* and -1.9 A along b* and c*. Anisotropic scale factors of B,, = -20.8 A', B,, = 7.4 A', B, = 13.3 A' corrected for the more rapid fall of diffraction in the a* direction. The anisotropy correlates with the weak crystal packing interactions along the a axis. In addition to apolar side chains in the protein core, there are 10 buried hydrogen bonding residues. Those residues involved in intramolecular hydrogen bonding to main chain atoms are better conserved than those hydrogen bonding to other side chain atoms; 24 solvation sites are observed at equivalent positions in the two molecules in the asymmetric unit, and the strongest among these are located in clefts between secondary structural elements. No buried water sites are seen. Two surface clusters of hydrophobic side chains are located near the expected receptor binding regions. Mutagenesis of 11 residues on the helix Nhelix C face confirms the importance of Glu-21 and shows that Gly-75 and Gln-86, located on helix C, each cause a greater than fourfold drop in activity. Glu-21 and Gly-75, but not Gln-86, are structurally equivalent to residues involved in the growth hormone binding to its receptor. 0 1996 Wiley-Liss, Inc.

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Novel Fold and Putative Receptor Binding Site of Granulocyte-Macrophage Colony-Stimulating Factor

Cited by 202 publications

References 31 publications

Hematopoietic cytokines: Similarities and differences in the structures, with implications for receptor binding

Hematopoietic cytokines: Similarities and differences in the structures, with implications for receptor binding

Computational simulations of stem-cell factor/c-Kit receptor interaction

Refined crystal structure and mutagenesis of human granulocyte-macrophage colony-stimulating factor

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