PDBsum entry 1wwc

Transferase

PDB id: 1wwc

Contents

Protein chain

105 a.a. *

Waters ×101

* Residue conservation analysis

PDB id:

1wwc

Name:

Transferase

Title:

Nt3 binding domain of human trkc receptor

Structure:

Protein (nt-3 growth factor receptor trkc). Chain: a. Fragment: ligand binding domain. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

1.90Å R-factor: 0.187 R-free: 0.288

Authors:

M.H.Ultsch,C.Wiesmann,L.C.Simmons,J.Henrich,M.Yang,D.Reilly,S.H.Bass, A.M.De Vos

Key ref:

M.H.Ultsch et al. (1999). Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and TrkC. J Mol Biol, 290, 149-159. PubMed id: 10388563 DOI: 10.1006/jmbi.1999.2816

Date:

30-Apr-99 Release date: 07-Jul-99

Protein chain

Q16288  (NTRK3_HUMAN) -  NT-3 growth factor receptor from Homo sapiens

Seq: 839 a.a.

Struc: 105 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1006/jmbi.1999.2816

J Mol Biol 290:149-159 (1999)

PubMed id: 10388563

Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and TrkC.

M.H.Ultsch, C.Wiesmann, L.C.Simmons, J.Henrich, M.Yang, D.Reilly, S.H.Bass, A.M.de Vos.

ABSTRACT

The Trk receptors and their neurotrophin ligands control development and maintenance of the nervous system. The crystal structures of the ligand binding domain of TrkA, TrkB, and TrkC were solved and refined to high resolution. The domains adopt an immunoglobulin-like fold, but crystallized in all three instances as dimers with the N-terminal strand of each molecule replaced by the same strand of a symmetry-related mate. Models of the correctly folded domains could be constructed by changing the position of a single residue, and the resulting model of the binding domain of TrkA is essentially identical with the bound structure as observed in a complex with nerve growth factor. An analysis of the existing mutagenesis data for TrkA and TrkC in light of these structures reveals the structural reasons for the specificity among the Trk receptors, and explains the underpinnings of the multi-functional ligands that have been reported. The overall structure of all three domains belongs to the I-set of immunoglobulin-like domains, but shows several unusual features, such as an exposed disulfide bridge linking two neighboring strands in the same beta-sheet. For all three domains, the residues that deviate from the standard fingerprint pattern common to the I-set family fall in the region of the ligand binding site observed in the complex. Therefore, identification of these deviations in the sequences of other immunoglobulin-like domain-containing receptors may help to identify their ligand binding site even in the absence of structural or mutagenesis data.

Selected figure(s)

Figure 2.
Figure 2. The relationship between the artifactual dimers and the modeled monomers. One monomer is colored red, the other green, and the hinge segment is shown in yellow. The residue whose position is affected by the remodeling is shown as a green or red dot. (a) Topology diagram of the ABED sheet observed in the crystal structures. (b) Topology of the ABED sheet after remodeling the AB loop.

Figure 3.
Figure 3. Models of the ligand- binding domain of the Trk recep- tors compared to the structure of telokin. The b-strands are shown as green arrows and labeled in TrkA- d5 and telokin, a helical segment is depicted as a red ribbon, and loops are colored yellow and labeled in TrkB-d5 and TrkC-d5. The exposed disulfide bridge connecting strands B and E in the Trk receptors is shown in ball-and-stick rendering. (a) TrkA-d5; (b) TrkB-d5; (c) TrkC- d5; (d) telokin, with the cysteine residues that usually (but not in tel- okin) form a buried disulfide bond shown in ball-and-stick rendering.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 290, 149-159) copyright 1999.

Figures were selected by an automated process.