The Complex Portal Birgit Meldal IntAct & Complex Portal Database Curator bmeldal@ebi.ac.uk www.ebi.ac.uk/complexportal @complexportal, @bmeldal

A couple of definitions… Protein-protein interactions (PPIs): physical and selective contacts that happen between pairs of proteins, in certain molecular regions and in a defined biological context. Protein A Protein B binds

A couple of definitions… Protein-protein interactions (PPIs): physical and selective contacts that happen between pairs of proteins, in certain molecular regions and in a defined biological context. Protein-protein interaction network (PPIN): Graphical representation of a group of PPIs in which proteins are represented as nodes and interactions as edges. A B

From Networks to Complexes PPI Networks can provide evidence for large structures that cannot be isolated in its entirety, e.g. Human proteasome Hook, B. and Schagat, T. [Internet] 2011. Available from: www.promega.com/resources/articles/pubhub/functional-proteomics-techniques-to-isolate-and-characterize-the-human-proteasome/

A complex entry has many source databases

A complex entry has many source databases

Common Curation pipeline & QC Sanity Checks (nightly) Release (monthly) reject Public web site FTP site accept annotate p1 p2 I exp Publication(s) (full text) . Web Service (complexes) CVs Curation manual check curator Super curator Other DBs report

Mission statement To provide freely accessible, high quality, manually curated annotations of macromolecular complexes.

Definition of a complex A stable set of (2 or more) interacting protein molecules which can be co-purified and have been shown to exist as a functional unit in vivo. Non-protein molecules (e.g. small molecules, nucleic acids) may also be present in the complex if they are an integral part of the complex.

What is not a stable complex? Enzyme/substrate, receptor/ligand or similar transient interactions, Unless: one element is a complex in its own right, and/or it is an obligate complex that requires substrate/ligand binding, maltose transporter requires maltose binding for holo-enzyme formation (EBI-6477643, EBI-8705175)

Maltose transport complex Core subunit, no maltose binding protein (MBP) or maltose Holo-enzyme with MBP and maltose (and ATP) EBI-8705175, 3fh6 EBI-6477643, 3puy

What is not a stable complex? Enzyme/substrate, receptor/ligand or similar transient interactions, Unless: one element is a complex in its own right, and/or it is an obligate complex that requires substrate/ligand binding, maltose transporter requires maltose binding for holo-enzyme formation (EBI-6477643, EBI-8705175) PDGF receptors: ligands are obligate dimer and receptors require ligand binding for dimerisation forming an obligate tetramer

PDGF receptor complex PMID:20534510: Fig. 2: Structure of the PDGF-B:PDGFRβ complex. (A) Side view of the ribbon model of the complex, with the PDGF-B protomers in green and blue, and the PDGFRβ protomers in pink and orange. The N-linked glycans attached to PDGFRβ are depicted as sticks. (B) Top view of the PDGF-B:PDGFRβ complex in surface representation.

What is not a stable complex? Enzyme/substrate, receptor/ligand or similar transient interactions, Unless: one element is a complex in its own right, and/or it is an obligate complex that requires substrate/ligand binding, maltose transporter requires maltose binding for holo-enzyme formation (EBI-6477643, EBI-8705175) PDGF receptors: ligands are obligate dimer and receptors require ligand binding for dimerisation forming an obligate tetramer Two proteins associated in a pulldown / coimmunoprecipitation with no functional link

Evidence Code Ontology

Evidence Code Ontology

Species coverage Arabidopsis thaliana Danio rerio

Complex search http://www.ebi.ac.uk/complexportal

Complex search http://www.ebi.ac.uk/complexportal Search examples Identifiers, names and synonyms of molecules (protein, gene, small molecule) Identifiers, names and synonyms of complexes Cross-references of complexes Species Gene Ontology terms

Complex search for all complexes (“*”) Filters: Species Biological role Molecule type

Demo: Overview of an entry Hemoglobin HbA EBI-9008420 Integrin alphaIIb-beta3 complex EBI-2554508 Shelterin EBI-10887677 Telomerase EBI-10045577 GO:0016491, EBI-9691559 PCNA EBI-1202920

Downloads via ftp From http://www.ebi.ac.uk/complexportal/download ftp://ftp.ebi.ac.uk/pub/databases/intact/complex/current/ Folder per species In PSI-XML 2.5 & 3.0  please use XML 3.0! ComplexTab – tab-del format

Web service REST-API http://www.ebi.ac.uk/intact/complex-ws/ 3 methods: ~/search/ ~/display/ ~/export/ Returns a JSON object Complex Viewer queries the WS for the JSON object

Curation Requests and Contact http://www.ebi.ac.uk/complexportal Found a bug? Report it! (GitHub) What to get updates? Sign up to our Newsletter or follow us on Twitter We tweet about releases, Complex of the Month (#CotM), usage tips and other curiosities Can’t find a complex? Request it! (generates email to helpdesk, will become a tracker)

A Service brought to you by EMBL-EBI in collaboration with… @ UCL Sandra Orchard Henning Hermjakob PDBe £ Max Koch past members… Noemi del Toro Ayllon Birgit Meldal

Thank you! ?