Linked Life Data

11842409

Source:http://linkedlifedata.com/resource/pubmed/id/11842409

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-2-13
pubmed:abstractText
The interactions of brain-derived neurotrophic factor (BDNF) with the extracellular domain of its receptor (trkB) are investigated by employing isotope-edited Fourier transform IR (FTIR) spectroscopy. The protein secondary structures of individual BDNF and trkB in solutions are compared with those in their complex. The temperature dependence of the secondary structures of BDNF, trkB, and their complex is also investigated. Consistent with the crystal structure, we observe by FTIR spectroscopy that BDNF in solution contains predominantly beta strands (approximately 53%) and relatively low contents of other secondary structures including beta turns (approximately 16%), disordered structures (approximately 12%), and loops (approximately 18%) and is deficient in alpha helix. We also observe that trkB in solution contains mostly beta strands (52%) and little alpha helix. Conformational changes in both BDNF and trkB are observed upon complex formation. Specifically, upon binding of BDNF, the conformational changes in trkB appear to involve mostly beta turns and disordered structures while the majority of the beta-strand conformation remains unchanged. The IR data indicate that some of the disordered structures in the loop regions are likely converted to beta strands upon complex formation. The FTIR spectral data of BDNF, trkB, and their complex indicate that more amide NH groups of trkB undergo H-D exchange within the complex than those of the ligand-free receptor and that the thermal stability of trkB is decreased slightly upon binding of BDNF. The FT-Raman spectra of BDNF, trkB, and their complex show that the six intramolecular disulfide bonds of trkB undergo significant conformational changes upon binding of BDNF as a result of changes in the tertiary structure of trkB. Taken together, the FTIR and Raman data are consistent with the loosening of the tertiary structure of trkB upon binding of BDNF, which leads to more solvent exposure of the amide NH group and decreased thermal stability of trkB. This finding reveals an intriguing structural property of the neurotrophin ligand-receptor complex that is in contrast to other ligand-receptor complexes such as a cytokine-receptor complex that usually shows protection of the amide NH group and increased thermal stability upon complex formation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0006-3525
pubmed:author
pubmed:copyrightInfo
Copyright 2002 John Wiley & Sons, Inc.
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11842409-Animals, pubmed-meshheading:11842409-Brain-Derived Neurotrophic Factor, pubmed-meshheading:11842409-CHO Cells, pubmed-meshheading:11842409-Carbon Isotopes, pubmed-meshheading:11842409-Cricetinae, pubmed-meshheading:11842409-Culture Media, Conditioned, pubmed-meshheading:11842409-Deuterium, pubmed-meshheading:11842409-Disulfides, pubmed-meshheading:11842409-Escherichia coli, pubmed-meshheading:11842409-Humans, pubmed-meshheading:11842409-Nitrogen Isotopes, pubmed-meshheading:11842409-Protein Conformation, pubmed-meshheading:11842409-Protein Structure, Secondary, pubmed-meshheading:11842409-Protein Structure, Tertiary, pubmed-meshheading:11842409-Receptor, trkB, pubmed-meshheading:11842409-Spectroscopy, Fourier Transform Infrared, pubmed-meshheading:11842409-Temperature, pubmed-meshheading:11842409-Transfection, pubmed-meshheading:11842409-Water
pubmed:year
2002
pubmed:articleTitle
Changes in protein conformation and dynamics upon complex formation of brain-derived neurotrophic factor and its receptor: investigation by isotope-edited Fourier transform IR spectroscopy.
pubmed:affiliation
Department of Pharmaceutics, Amgen Inc., Amgen Center, M/S 8-1-C, One Amgen Boulevard, Thousand Oaks, California 91320, USA. tli@amgen.com
pubmed:publicationType
Journal Article, Comparative Study