NGF Structure

NGF Structure of Monomer

Nerve growth factor (NGF), discovered almost sixty years ago, is the founding and best-characterized member of the neurotrophin family. In 1991, NGF structure was determined by X-ray crystallography. NGF structure has represented a novel protein fold. NGF structure of monomer has an elongated shape with the central part of the molecule formed by two pairs of twisted, antiparallel β-strands. There are three hairpin loops on one end of NGF structure. The other end carries a cysteine-knot motif that stabilizes the fold and locks the molecules in their conformation. NGF structure of monomer can be seen in figure 1.

NGF Structure of Biologically Active Form

When NGF performs its biological activity, NGF is arranged in a parallel manner to form a close-packed homodimer. These two monomers assemble around a central twofold axis. The long axis of NGF structure coincides with the twofold axis. NGF structure of biologically active form is given an overall dumbbell-like shape. The two central b sheets of the two monomers pack against each other and form the 'handle' of the dumbbell. Residues from these four b strands are responsible for the majority of interactions that stabilize the dimer. The cysteine-knot motif, the N and C termini, and the third loop connecting strands B and C form one end of the dumbbell, now shown by the crystal structure of the NGF-TrkA domain 5 complex to be pointing away from the membrane. The other, membrane-facing end contains three hairpin loops as well as four short b strands arranged in two antiparallel β sheets. NGF structure of dimer can be seen in figure2.

7S NGF Structure

In Mouse submaxillay, NGF is isolated from gland homogenates as a high molecular weight complex containing three types of polypeptide chains. These three chains of NGF structure are designates α,β and γ. The complex contains two copies of each component, yielding an α2βγ2-stoichiometry symmetrically arranged around a two-fold symmetry axis relating the two NGF molecules (fig.3) . The molecular weight of either the α- andγ- subunits is approximately 26,000 Da while the combined molecular weight of the two polypeptides of the β-subunit is 26518 Da. Of the three subunits, only the β-moiety possesses nerve growth promoting activity and it is solely responsible for the maintenance of adrenergic neurons in vitro whileα-NGF and γ-NGF are two related serine proteases of the kallikrein family. γ-NGF is a highly specific, active protease, capable of processing the pre-NGF to its mature form, α-NGF is inactive and has been described as a 'locked zymogen'. The complex is stabilized by two zinc ions that bind in the interfaces between NGF and γ-NGF. The NGF dimer is in contact with both copies of the α- and γ-NGF molecules. The α-NGF molecules are bound to the central portion of NGF, partially overlapping the 'conserved patch' of the Trk receptor-binding site. Interestingly, the NGF C terminus is bound in the active site of the protease. While there are no contacts between the two α-NGF molecules, the two γ-NGF molecules have an extensive interface with each other. This interface is over 2500 Å2 in area and likely to contribute significant stabilization to the overall complex. However, this interaction is not sufficient to stabilize γ-NGF dimers in the absence of NGF, since free γ-NGF is monomeric in solution. NGF structure of 7S NGF can be seen in figure3.

The structure of NGF monomer

Figure 1: The structure of NGF monomer (PDB:1BFT)

The structure of NGF dimer

Figure 2: The structure of NGF dimer (PDB:1BET)

The structure of 7S NGF

Figure 3: The structure of 7S NGF (PDB: ISGF)

23000+ Products
cDNA Clones
Recombinant Cytokines
Neurotrophin & Receptor
NGF Related Information +
- NGF molecular weight
- NGF structure
- NGF function
- NGF signaling / pathway
- NGF receptor
-- NGF TrkA
-- NGFR / p75
BDNF Related Information +
- BDNF Gene
- BDNF function
- BDNF signaling / pathway
- BDNF receptor
-- BDNF TrkB
-- NGFR / p75
• Other Neurotrophin & Receptor+
- Neurotrophin-3 / NT-3
- TrkA / NTRK1
- TrkB / NTRK2
- TrkC / NTRK3
- NGFR (p75 / p75 NTR)
GDNF Family
GDNF (Glial cell line-derived neurotrophin)
Other Neurotrophic Factors & Receptors
Gp130 / IL6ST
LIFR / CD118
CNTF / Ciliary Neurotrophic Factor
NRG1 / Neuregulin 1
NRG4 / Neuregulin 4
Pleiotrophin / PTN
Growth Factor Family
Ephrin & Eph Receptor
EGF & Receptor
FGF & Receptor
Insulin-like Growth Factor System
Neurotrophin & Receptor
PDGF & Receptor
Receptor Tyrosine Kinase
R-Spondin Protein
VEGF & Receptor
Wnt Ligands & Receptors