PMID- 11855816
OWN - NLM
STAT- MEDLINE
DCOM- 20020401
LR  - 20161124
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 291
IP  - 3
DP  - 2002 Mar 1
TI  - A discrete domain of the human TrkB receptor defines the binding sites for BDNF 
      and NT-4.
PG  - 501-7
AB  - TrkB is a member of the Trk family of tyrosine kinase receptors. In vivo, the 
      extracellular region of TrkB is known to bind, with high affinity, the 
      neurotrophin protein brain-derived neurotrophic factor (BDNF) and neurotrophin-4 
      (NT-4). We describe the expression and purification of the second Ig-like domain 
      of human TrkB (TrkBIg(2)) and show, using surface plasmon resonance, that this 
      domain is sufficient to bind BDNF and NT-4 with subnanomolar affinity. BDNF and 
      NT-4 may have therapeutic implications for a variety of neurodegenerative 
      diseases. The specificity of binding of the neurotrophins to their receptor TrkB 
      is therefore of interest. We examine the specificity of TrkBIg(2) for all the 
      neurotrophins, and use our molecular model of the BDNF-TrkBIg(2) complex to 
      examine the residues involved in binding. It is hoped that the understanding of 
      specific interactions will allow design of small molecule neurotrophin mimetics.
CI  - (c)2002 Elsevier Science (USA).
FAU - Naylor, Ruth L
AU  - Naylor RL
AD  - University Research Centre for Neuroendocrinology (Care of the Elderly), Bristol 
      Royal Infirmary, Bristol, BS2 8HW, United Kingdom.
FAU - Robertson, Alan G S
AU  - Robertson AG
FAU - Allen, Shelley J
AU  - Allen SJ
FAU - Sessions, Richard B
AU  - Sessions RB
FAU - Clarke, Anthony R
AU  - Clarke AR
FAU - Mason, Grant G F
AU  - Mason GG
FAU - Burston, Judy J
AU  - Burston JJ
FAU - Tyler, Sue J
AU  - Tyler SJ
FAU - Wilcock, Gordon K
AU  - Wilcock GK
FAU - Dawbarn, David
AU  - Dawbarn D
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Immunoglobulin Fragments)
RN  - 0 (Nerve Growth Factors)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Circular Dichroism
MH  - Humans
MH  - Immunoglobulin Fragments/chemistry
MH  - Kinetics
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Nerve Growth Factors/*metabolism
MH  - Protein Structure, Tertiary
MH  - Receptor, trkB/*chemistry/isolation & purification/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
MH  - Surface Plasmon Resonance
EDAT- 2002/02/22 10:00
MHDA- 2002/04/02 10:01
CRDT- 2002/02/22 10:00
PHST- 2002/02/22 10:00 [pubmed]
PHST- 2002/04/02 10:01 [medline]
PHST- 2002/02/22 10:00 [entrez]
AID - S0006291X02964685 [pii]
AID - 10.1006/bbrc.2002.6468 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2002 Mar 1;291(3):501-7. doi: 10.1006/bbrc.2002.6468.