Issues raised by the curation of complexes. Sylvie Ricard-Blum UMR 5086 CNRS-Université Lyon 1 Lyon, France
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1 Issues raised by the curation of complexes Sylvie Ricard-Blum UMR 5086 CNRS-Université Lyon 1 Lyon, France
2 Extracellular proteins The core matrisome 300 proteins* ECM-affiliated proteins 800 proteins Poorly soluble, very large, proteins Often multimers (trimers, pentamers) (*Naba et al. Mol Biol Cell Jan 19, Hynes and Naba Cold Spring Harb Perspect Biol :a004903, Peysselon et al; 2012 in Hyaluronan, From Basic Science to Clinical Applications, structure and Function of Biomatrix, EA Balazs ed. Matrix Biology institute, USA )
3 Extracellular multimeric proteins Thrombospondins (5) Laminins (16) Collagens (28) Native molecules are homotrimers or heterotrimers
4 Extracellular multimeric proteins Native molecules secreted and found in tissues as multimers Biological entities Different interaction repertoires for individual polypeptide chains and for multimers
5 Receptors of extracellular proteins Integrins (24) Discoidin domain receptors (2) Dimers (Leitinger Annu. Rev. Cell Dev. Biol :265 90)
6 86 EBI-identifiers used in MatrixDB Permanent complexes MatrixDB identifier: MULT_x EBI identifier: EBI-xxxxxxx for human proteins so far - Collagens - Laminins - Thrombospondins Created by Sandra Orchard - Integrins More to be added: other species, other ECM or ECM-affiliated proteins e.g. growth factors (source: UniProtKB)
7
8 EBI-identifiers used in MatrixDB The list will be available on the updated website of Will other databases use these identifiers for curation? Should the list be available on IMEx website?
9 Curation tool box for extracellular interactions Mutants Endostatin mutants Posted on the web site Constructs widely used to express extracellular protein fragments Fibrillin Elastin (Cain et al Mol Cell Proteomics 8: )
10 Multimers in innate immunity Collectins: trimers Ficolins: trimers C1q: a complex complex (Ghebrehiwet et al. Frontiers Immunol 2012 Apr 5;3. doi:pii: 52)
11 The structural organization of the C1q complex Complement C1q subcomponent subunit A Complement C1q subcomponent subunit B Complement C1q subcomponent subunit C P02745 P02746 P02747 (Ghebrehiwet et al. Frontiers Immunol 2012 Apr 5;3. doi:pii: 52)
12 The structural organization of the C1q complex C1q subcomponent is composed of nine subunits, six of which are disulfide-linked dimers of the A and B chains, and three of which are disulfide-linked dimers of the C chain (Ghebrehiwet et al. Frontiers Immunol 2012 Apr 5;3. doi:pii: 52)
13 C1, a trimolecular complex of C1q, C1r and C1s C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system C1 is a calcium-dependent trimolecular complex of C1q, R and S in the molar ration of 1:2:2 (Arlaud et al Mol Immunol 39: )
14 Fibrinogen Fibrinogen alpha chain Fibrinogen beta chain Fibrinogen gamma chain P02671 P02675 P02679 General annotation Heterohexamer; disulfide linked. Contains 2 sets of 3 non-identical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain
15 The region E of fibrinogen, a complex issued from processed complex? Fibrinogen consists of 2 identical disulfide-linked subunits, each of which is formed by 3 different polypeptide chains The central E region is a chemical dimer formed by the NH 2 - terminal portions of all 6 chains (Yakovlev et al Biochemistry 42: )
16 Tentative classification of complexes Permanent complexes corresponding to native, functional, proteins Resulting from the quaternary structure of proteins Association of several subunits (or polypeptide chains) that form a functional protein Isolated subunits do not have a biological function Examples: hemoglobin (insulin, collagens, laminins, C1q) Participants: complexes in the curation process?
17 Tentative classification of complexes Context-dependent complexes corresponding to multiprotein complexes Resulting from the association of several proteins Isolated proteins might have a biological function, either alone or in association with several proteins Isolated proteins can belong to different complexes Examples: C1 = C1q + C1s + C1r, proteasome, fatty acid synthetase complex, photosynthets) Participants: complexes in the curation process
18 Next on the list, the fibrils Collagen fibrils Amyloid fibrils
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