1BND

STRUCTURE OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR(SLASH)NEUROTROPHIN 3 HETERODIMER


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Work: 0.182 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure of the brain-derived neurotrophic factor/neurotrophin 3 heterodimer.

Robinson, R.C.Radziejewski, C.Stuart, D.I.Jones, E.Y.

(1995) Biochemistry 34: 4139-4146

  • DOI: https://doi.org/10.1021/bi00013a001
  • Primary Citation of Related Structures:  
    1BND

  • PubMed Abstract: 

    The development and sustenance of specific neuronal populations in the peripheral and central nervous systems are controlled through the binding of neurotrophic factors to high-affinity cell surface receptors. The neurotrophins (nerve growth factor, NGF; brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT3; and neurotrophin 4, NT4) are dimeric molecules which share approximately 50% sequence identity. The crystal structure of the murine NGF homodimer [McDonald et al. (1991) Nature 354, 411-414] indicated that the dimer interface corresponds to regions of high sequence conservation throughout the neurotrophin family. This potential compatibility was duly exploited for the production in vitro of noncovalent heterodimers between the different neurotrophins [Radziejewski, C., & Robinson, R.C. (1993) Biochemistry 32, 13350-13356; Jungbluth et al. (1994) Eur. J. Biochem. 221, 677-685]. Here, we report the X-ray structure at 2.3 A resolution of one such heterodimer, between human BDNF, and human NT3. The NGF, BDNF, and NT3 protomers share the same topology and are structurally equivalent in regions which contribute to the dimer interface in line with the propensity of the neurotrophins to form heterodimers. Analysis of the structure of regions of the BDNF/NT3 heterodimer involved in receptor specificity led us to conclude that heterodimer binding to p75 involves distant binding sites separately located on each protomer of the heterodimer. In contrast, heterodimer interactions with the trk receptors probably utilize hybrid binding sites comprised of residues contributed by both protomers in the heterodimer. The existence of such hybrid binding sites for the trk receptor provides an explanation for the lower activity of the BDNF/NT3 heterodimer in comparison to the homodimers.(ABSTRACT TRUNCATED AT 250 WORDS)


  • Organizational Affiliation

    Laboratory of Molecular Biophysics, Oxford University, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BRAIN DERIVED NEUROTROPHIC FACTOR119Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P23560 (Homo sapiens)
Explore P23560 
Go to UniProtKB:  P23560
PHAROS:  P23560
GTEx:  ENSG00000176697 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23560
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
NEUROTROPHIN 3119Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P20783 (Homo sapiens)
Explore P20783 
Go to UniProtKB:  P20783
PHAROS:  P20783
GTEx:  ENSG00000185652 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP20783
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IPA
Query on IPA

Download Ideal Coordinates CCD File 
C [auth A]ISOPROPYL ALCOHOL
C3 H8 O
KFZMGEQAYNKOFK-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Work: 0.182 
  • R-Value Observed: 0.182 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 98.4α = 90
b = 45.1β = 118.3
c = 68γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
X-PLORmodel building
X-PLORrefinement
X-PLORphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1996-04-04
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance