Molecular modeling of human granulocyte-macrophage colony-stimulating factor.
The colony-stimulating factors (CSFs) are a group of acidic glycoproteins which are required for the proliferation of hematopoietic progenitor cells and for their differentiation into mature blood cells. Receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) are present on a wide spectrum of cells including erythroid, mixed erythroid-non-erythroid, mixed myeloid and megakaryocytic progenitors, and on mature neutrophils, eosinophils and monocytes. A number of studies are now available which provide insights into the structure-function relationships of human GM-CSF. In an attempt to further understand the interaction between GM-CSF and its cell surface receptor, we have constructed models of the tertiary structure of human GM-CSF using the known disulfide bonding pattern, predictions of the secondary structure of the growth factor and a model based on conformational homologies among cytokines (Parry et al., J Mol Recognition 1988;1:107-110). When compared to a number of functional mapping studies, structural features of the model are consistent with the experimental data, and the model, in turn, leads to the generation of a number of testable hypotheses. The implications of these features in terms of receptor-ligand interaction are discussed.
Kaushansky
K
K
Division of Hematology, University of Washington, Seattle 98195.
Brown
C B
CB
O'Hara
P J
PJ
D000465:Algorithms; D000818:Animals; D001685:Biological Factors; D003115:Colony-Stimulating Factors; D003196:Computer Graphics; D016207:Cytokines; D004220:Disulfides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D011994:Recombinant Proteins; D012984:Software; D013329:Structure-Activity Relationship
D001685:Biological Factors; D003115:Colony-Stimulating Factors; D016207:Cytokines; D004220:Disulfides; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor