Chimeric molecules with multiple neurotrophic activities reveal structural elements determining the specificities of NGF and BDNF.
Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are two members of a family of neurotrophic factors which show both overlapping and distinct neurotrophic activities. Using site-directed mutagenesis, chimeric molecules were constructed where different combinations of sequences from BDNF replaced the corresponding sequences in NGF. The resulting molecules were transiently expressed in COS cells and conditioned media containing the chimeric proteins were assayed for biological activity in explanted chick sympathetic, spinal and nodose ganglia. Our results show that the biological specificities of the two proteins are obtained by specific combinations of a set of sequences that differ between the two molecules. Some of these combinations allowed us to engineer molecules which display multiple neurotrophic activities recruited from both the NGF and BDNF proteins.
Ibáñez
C F
CF
Department of Medical Chemistry, Karolinska Institute, Stockholm, Sweden.
Ebendal
T
T
Persson
H
H
D000595:Amino Acid Sequence; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002460:Cell Line; D002642:Chick Embryo; D004247:DNA / Q000235:genetics; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D019208:Brain-Derived Neurotrophic Factor; D006133:Growth Substances; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C019277:brain-derived growth factor; D004247:DNA