ProtSkin analysis of PTPs

Provided a structure file and an alignment of homologous sequences, the ProtSkin server maps the degree of sequence identity (or similarity) onto a protein structure to visualize conserved/non-conserved regions. (See the section on Bioinformatics Links for details).

Sequence conservation scores for 37 human PTP domains

Surface representation of PTP1B colored by conservation scores (blue, most conserved; red, least conserved). Scores are based on 37 aligned human PTP domains and reflect sequence identity to PTP1B (PDB identifier: 1G1H; see ProtSkin for details).

PDF Format | Powerpoint Format

Note that both conserved and non-conserved residues are involved in substrate recognition of the bis-phosphorylated insulin receptor (IR). Compare for example the difference in conservation scores for Arg24 and Arg254, two residues in PTP1B that both form salt bridge interactions with the phosphate group of pTyr1163 of the IR peptide). Other less well-conserved PTP1B residues involved in substrate recognition include Arg47, Asp48, Phe192 and G259. Below we provide session files of the analysis for simple viewing on a PC or Mac (requires PyMol).

Ramp Mode | Histogram Mode

Elements unique to PTP1B substrate recognition visualized by structural superimposition

Superimposition of the PTP1B/IR-peptide complex (PTP1B, orange; IR, green) with PTPµ domain D1 (grey). The PTP active site and the ‘second site’ of PTP1B are highlighted to show that the presence of a bulky residue in PTPµ (Asn1136), at the position occupied by Gly259 in PTP1B, prevents PTPµ from recognizing two adjacent pTyr residues.

PDF Format | Powerpoint Format | PyMol Session File

ProtSkin analysis suggests unique functions for PTP domains D1 and D2 and identifies conserved residues at the interface

To map conservation scores onto protein structure, we submitted an alignment of 63 full-length tandem domain (D1D2) sequences and the X-ray crystal structure of LAR (PDB identifier: 1LAR) to the ProtSkin server. The output file from the server was colored according to its conservation scores (i.e. b-values) using PyMol and the ‘color_b.py’ script (histogram mode).

PDF Format | Powerpoint Format

Here, we provide session files of the analysis for simple viewing on a PC or Mac (requires PyMol installation).

PyMol Fig. 6A | Fig. 6B | Fig. 6C

Also we provide a Zip file of the script used to generate Figure 6A-C (Methods 2005).