PDBsum entry: 1xr0

Signaling protein/growth factor receptor

PDB id: 1xr0

Contents

Protein chains

22 a.a.

129 a.a. *

* Residue conservation analysis

PDB id:

1xr0

Name:

Signaling protein/growth factor receptor

Title:

Structural basis of snt ptb domain interactions with distinct neurotrophic receptors

Structure:

Basic fibroblast growth factor receptor 1. Chain: a. Fragment: sequence database residues 409-430 from the juxtamembrane region of hfgfr1. Synonym: fgfr-1, bfgf-r, fms-like tyrosine kinase-2, c-fgr. Engineered: yes. Fgfr signalling adaptor snt-1. Chain: b. Fragment: ptb domain at the n terminus.

Source:

Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence is taken from homo sapiens (human).. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

NMR struc:

1 models

Authors:

C.Dhalluin,K.S.Yan,O.Plotnikova,K.W.Lee,L.Zeng,M.Kuti, S.Mujtaba,M.P.Goldfarb,M.-M.Zhou

Key ref:

C.Dhalluin et al. (2000). Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors. Mol Cell, 6, 921-929. PubMed id: 11090629 DOI: 10.1016/S1097-2765(05)00087-0

Date:

13-Oct-04 Release date: 02-Nov-04

Protein chain

P11362  (FGFR1_HUMAN) -  Fibroblast growth factor receptor 1

Seq: 822 a.a.

Struc: 22 a.a.

Protein chain

Q8WU20  (FRS2_HUMAN) -  Fibroblast growth factor receptor substrate 2

Seq: 508 a.a.

Struc: 129 a.a.*

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

Enzyme reactions

• Enzyme class: Chain A: E.C.2.7.10.1 - Receptor protein-tyrosine kinase.
• Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

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

 Gene Ontology (GO) functional annotation 

• Biochemical function: insulin receptor binding (1 term)

reference

DOI no: 10.1016/S1097-2765(05)00087-0

Mol Cell 6:921-929 (2000)

PubMed id: 11090629

Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors.

C.Dhalluin, K.S.Yan, O.Plotnikova, K.W.Lee, L.Zeng, M.Kuti, S.Mujtaba, M.P.Goldfarb, M.M.Zhou.

ABSTRACT

SNT adaptor proteins transduce activation of fibroblast growth factor receptors (FGFRs) and neurotrophin receptors (TRKs) to common signaling targets. The SNT-1 phosphotyrosine binding (PTB) domain recognizes activated TRKs at a canonical NPXpY motif and, atypically, binds to nonphosphorylated FGFRs in a region lacking tyrosine or asparagine. Here, using NMR and mutational analyses, we show that the PTB domain utilizes distinct sets of amino acid residues to interact with FGFRs or TRKs in a mutually exclusive manner. The FGFR1 peptide wraps around the beta sandwich structure of the PTB domain, and its binding is possibly regulated by conformational change of a unique C-terminal beta strand in the protein. Our results suggest mechanisms by which SNTs serve as molecular switches to mediate the essential interplay between FGFR and TRK signaling during neuronal differentiation.

Selected figure(s)

Figure 2.
Figure 2. Structure of the SNT-1 PTB Domain/hFGFR1 Complex(A) Stereoview of the backbone atom superposition of the final 20 NMR-derived structures of the complex. The figure shows the SNT-1 PTB domain residues 18–116 and the hFGFR1 peptide residues 411–430. The terminal residues, which are structurally disordered, are omitted for clarity. For the final 20 structures, the root-mean-square deviations (rmsd) of the backbone and all heavy atoms for protein residues 18–116 are 0.74 ± 0.16 Å and 1.46 ± 0.16 Å, respectively. The corresponding rmsd for the protein secondary-structural regions (protein residues 19–24, 35–40, 45–49, 52–57, 63–68, 71–76, 85–90, 94–107, and 111–115) are 0.40 ± 0.05 Å and 0.88 ± 0.05 Å, respectively. The rmsd of the backbone and all heavy atoms for the hFGFR1 peptide (residues 412–430) are 0.56 ± 0.10 Å and 1.25 ± 0.15 Å, respectively.(B) Ribbons () depiction of the averaged minimized NMR structure of the SNT-1 PTB domain/hFGFR1 complex. The orientation of (B) is as shown in (A).(C) Ribbon diagram of the SNT-1 PTB domain structure from the top of the protein, which is rotated vert, similar 90° from the orientation in (B).(D) Molecular surface representation of the SNT-1 PTB domain structure calculated in GRASP ([[5]24]). The protein is color coded by surface curvature, and the color gradient from green to dark gray reflects decreasing solvent exposure. The hFGFR1 peptide molecule is shown as a ball-and-stick representation color coded by atom type.

Figure 4.

The above figures are reprinted by permission from Cell Press: Mol Cell (2000, 6, 921-929) copyright 2000.

Figures were selected by the author.