|1b98, resolution 2.75Å ()|
NEUROTROPHIN 4 (HOMODIMER)
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.
The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site., Robinson RC, Radziejewski C, Spraggon G, Greenwald J, Kostura MR, Burtnick LD, Stuart DI, Choe S, Jones EY, Protein Sci. 1999 Dec;8(12):2589-97. PMID:10631974
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[NTF4_HUMAN] Defects in NTF4 may be associated with susceptibility to primary open angle glaucoma type 1O (GLC1O) [MIM:613100]. A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. The disease is asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place.
[NTF4_HUMAN] Target-derived survival factor for peripheral sensory sympathetic neurons.
About this Structure
1b98 is a 2 chain structure with sequence from Homo sapiens. The August 2005 RCSB PDB Molecule of the Month feature on Neurotrophins by David S. Goodsell is 10.2210/rcsb_pdb/mom_2005_8. Full crystallographic information is available from OCA.
- 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 Dec;8(12):2589-97. PMID:10631974