MF2201009
Brain-derived neurotrophic factor/neurotrophin 4 heterodimer
1b8m
X-ray
2.75
heterodimer
Sus scrofa / Homo sapiens
10631974
Robinson RC, Radziejewski C, Spraggon G, Greenwald J, Kostura MR, Burtnick LD, Stuart DI, Choe S, Jones EY
The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site.
Protein Sci.
1999
12
8
2589-97
The neurotrophins are growth factors that are involved in the development and survival of neurons. Neurotrophin release by a target tissue results in neuron growth along the neurotrophin concentration gradient, culminating in the eventual innervation of the target tissue. These activities are mediated through trk cell surface receptors. We have determined the structures of the heterodimer formed between brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT4), as well as the structure of homodimer of NT4. We also present the structure of the Neurotrophin 3 homodimer, which is refined to higher resolution than previously published. These structures provide the first views of the architecture of the NT4 protomer. Comparison of the surface of a model of the BDNF homodimer with the structures of the neurotrophin homodimers reveals common features that may be important in the binding between the neurotrophins and their receptors. In particular, there exists an analogous region on the surface of each neurotrophin that is likely to be involved in trk receptor binding. Variations in sequence on the periphery of this common region serve to confer trk receptor specificity.
GO:0008083
growth factor activity
GO:0007169
transmembrane receptor protein tyrosine kinase signaling pathway
GO:0045664
regulation of neuron differentiation
GO:0007267
cell-cell signaling
GO:0048812
neuron projection morphogenesis
GO:0043524
negative regulation of neuron apoptotic process
GO:0016023
cytoplasmic, membrane-bounded vesicle
GO:0005576
extracellular region
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
NGF-like proteins
Heterodimeric NGF-like proteins
A
Brain-derived neurotrophic factor
Sus scrofa
HSDPARRGELSVCDSISEWVTAADKKTAVDMSGGTVTVLEKVPVSKGQLKQYFYETKCNPMGYTKEGCRGIDKRHWNSQCRTTQSYVRALTMDSKKRIGWRFIRIDTSCVCTLTIKRGR
119
P14082
134
252
47.2%
UniRef90_P23560-3
144
262
secondary structure
beta
144
144
secondary structure
beta
148
154
secondary structure
helix
155
158
secondary structure
beta
160
163
secondary structure
beta
168
171
secondary structure
beta
174
177
secondary structure
beta
180
183
secondary structure
beta
185
191
secondary structure
beta
204
204
secondary structure
beta
210
225
secondary structure
beta
231
247
pfam
PF00243.15
NGF
138
251
B
Neurotrophin-4
Homo sapiens
GVSETAPASRRGELAVCDAVSGWVTDRRTAVDLRGREVEVLGEVPAAGGSPLRQYFFETRCKADNAEEGGPGAGGGGCRGVDRRHWVSECKAKQSYVRALTADAQGRVGWRWIRIDTACVCTLLSRTGRA
130
P34130
81
210
61.9%
UniRef90_P34130
81
210
secondary structure
beta
93
95
secondary structure
beta
99
104
secondary structure
beta
109
112
secondary structure
beta
117
120
secondary structure
beta
123
124
secondary structure
beta
132
133
secondary structure
beta
136
141
secondary structure
beta
161
161
secondary structure
beta
167
182
secondary structure
beta
188
205
pfam
PF00243.15
NGF
89
208
Various dimeric members of neurotrophic factors (including human/mouse nerve growth factor, human brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5)) have been shown to fold and dimerize at the same time via a two-state process (PMID:8161524). While the members of this family show a significant variance in sequence, they adopt a highly similar structure upon binding and behave almost identically in unfolding/refolding experiments. Thus the two-state folding/binding nature seems to be a hallmark of NGF and closely related proteins.