Examples demonstrating how DILIMOT works

To better understand what DILIMOT can do, we've provided a few examples for people to try.

SH3 domain interaction partners

Src homology 3 (SH3) domains play important roles in signalling by mediating a wide variety of protein-protein interactions. After several years of experimental research it was deduced that they recognised short, proline rich segments within other proteins. The SH3 example sequences are a set of known SH3 binding proteins extracted by inspection of known three-dimensional structures. The server will return various proline rich motifs, most of which contain the canonical PxxP pattern. More information about SH3 motifs can be found at the ELM server.

The PCNA interaction motif

Proliferating Cell Nuclear Antigen (PCNA) has long been known to bind to the rather unusual QxxxxxFF motif as part of its role in regulating DNA replication, repair, methylation and the cell-cycle. Submitting a set of PCNA interaction partners will give variations around the QxxxxxFF theme. More information about PCNA motifs can be found at the ELM server.

The Translin binding motif

Translin is not a very well understood protein in terms of function. It forms a multimeric ring like structure that binds to single stranded RNA and DNA molecules, and is thought to be involved in chromosomal rearrangements. Several interaction partners of Translin were uncovered during a genome-scale yeast two hybrid screen using Drosophila proteins, and when these translin interacting sequences are submitted to the server they should return variations around the VxxxRxYS sequence, that we predicted and showed that peptides containing it bound directly to the Tranlin molecule

A new Protein Phosphatase 1 binding motif

Protein phosphatase 1 (PP1) or Calcineurin (in human) has long been known to bind proteins containing an RVxF motif. We re-discovered this motif in Drosophila interactions, but in Yeast proteins we also found a highly acidic DxxDxxxD pattern in several PP1 interactors. Peptides containing this motif also showed direct binding to PP1 when we tested them. Submitting these PP1 Yeast interation partners should give variations on this motif.

The MAP kinase Lit-1 binding moitf

Genome scale yeast two-hybrid studies with C. elegans proteins found several interaction partners of this MAP kinase, including several previously established (e.g. mom-4, wrm-1 and pop-1) plus numerous novel interactors. Within these Lit-1 interation partners we found a SxPxxxS pattern. Previously, deletions of segments containing, or immediately adjacent to instances of these motifs (in mom-4, wrm-1 & pop-1) were found to block the interaction with lit-1. The server should return this motif among several others, including other possible promising candidates like PLxIxT.

More details can be found in:

V. Neduva, R. Linding, I. Su-Angrand, A. Stark, F. de Massi, T.J. Gibson, J. Lewis, L. Serrano, R.B. Russell, Systematic discovery of peptides mediating protein interaction networks PLoS Biology, 3, e405 2005.
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