PDBsum entry 1b98

Hormone/growth factor

PDB id

1b98

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Contents

			Protein chains

					103 a.a. *


					113 a.a. *

			Metals

					_CL

			Waters ×49

* Residue conservation analysis

PDB id:

1b98

Links

Name:

Hormone/growth factor

Title:

Neurotrophin 4 (homodimer)

Structure:

Protein (neurotrophin-4). Chain: a, m. Fragment: precursor residues 81-210. Synonym: nt4. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: supplied by regeneron pharmacuticals

Biol. unit:

Dimer (from PQS)

Resolution:

2.75Å

R-factor:

0.235

R-free:

0.336

Authors:

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

Key ref:

R.C.Robinson et al. (1999). The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site. Protein Sci, 8, 2589-2597. PubMed id: 10631974 DOI: 10.1110/ps.8.12.2589

Date:

22-Feb-99

Release date:

26-Feb-99

PROCHECK

	Headers

	References

Protein chain

P34130 (NTF4_HUMAN) - Neurotrophin-4 from Homo sapiens

Seq: Struc:					210 a.a. 103 a.a.

Protein chain

P34130 (NTF4_HUMAN) - Neurotrophin-4 from Homo sapiens

Seq: Struc:					210 a.a. 113 a.a.

Key:

PfamA domain

Secondary structure

CATH domain

DOI no: 10.1110/ps.8.12.2589	Protein Sci 8:2589-2597 (1999)
PubMed id: 10631974

The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site.
R.C.Robinson, C.Radziejewski, G.Spraggon, J.Greenwald, M.R.Kostura, L.D.Burtnick, D.I.Stuart, S.Choe, E.Y.Jones.

ABSTRACT

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.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20408815

J.J.Buckley, S.D.Hoeltzli, and G.V.Johnson (2010).
Development of a rapid, high-efficiency, scalable refold for neurotrophin-4.

Biotechnol Appl Biochem, 56, 27-34.

19765683

F.Pasutto, T.Matsumoto, C.Y.Mardin, H.Sticht, J.H.Brandstätter, K.Michels-Rautenstrauss, N.Weisschuh, E.Gramer, W.D.Ramdas, L.M.van Koolwijk, C.C.Klaver, J.R.Vingerling, B.H.Weber, F.E.Kruse, B.Rautenstrauss, Y.A.Barde, and A.Reis (2009).
Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open-angle glaucoma.

Am J Hum Genet, 85, 447-456.

19721188

S.J.O'Leary, R.R.Richardson, and H.J.McDermott (2009).
Principles of design and biological approaches for improving the selectivity of cochlear implant electrodes.

J Neural Eng, 6, 55002.

18809686

J.M.Fletcher, C.J.Morton, R.A.Zwar, S.S.Murray, P.D.O'Leary, and R.A.Hughes (2008).
Design of a conformationally defined and proteolytically stable circular mimetic of brain-derived neurotrophic factor.

J Biol Chem, 283, 33375-33383.

16680799

J.M.Fletcher, and R.A.Hughes (2006).
Novel monocyclic and bicyclic loop mimetics of brain-derived neurotrophic factor.

J Pept Sci, 12, 515-524.

12676795

E.J.Huang, and L.F.Reichardt (2003).
Trk receptors: roles in neuronal signal transduction.

Annu Rev Biochem, 72, 609-642.

11520916

E.J.Huang, and L.F.Reichardt (2001).
Neurotrophins: roles in neuronal development and function.

Annu Rev Neurosci, 24, 677-736.

11520933

M.V.Sofroniew, C.L.Howe, and W.C.Mobley (2001).
Nerve growth factor signaling, neuroprotection, and neural repair.

Annu Rev Neurosci, 24, 1217-1281.

11574464

S.G.Hymowitz, E.H.Filvaroff, J.P.Yin, J.Lee, L.Cai, P.Risser, M.Maruoka, W.Mao, J.Foster, R.F.Kelley, G.Pan, A.L.Gurney, A.M.de Vos, and M.A.Starovasnik (2001).
IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding.

EMBO J, 20, 5332-5341.

PDB code:

1jpy

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.