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Structures of protein-protein interactions: zoom lens to the cell

Structures of protein-protein interactions: zoom lens to the cell. Ricardo C. Rodríguez de la Vega Universit é Paris-Sud Orsay, France. Big numbers in the –omes age.

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Structures of protein-protein interactions: zoom lens to the cell

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  1. Structures of protein-protein interactions: zoom lens to the cell Ricardo C. Rodríguez de la Vega Université Paris-Sud Orsay, France

  2. Big numbers in the –omes age Experimental biology is generating data at an incredible pace. Just an example: in less than 20 years we went from the first fully sequenced genome (Heamophilus influenzae in 1995, size: 1.8 Mb) to the almost 7,000 complete available today (collectively accounting for more than 300 Gb).

  3. Big numbers in the –omes age Experimental biology is generating data at an incredible pace. Just an example: in less than 20 years we went from the first fully sequenced genome (Heamophilus influenzae in 1995, size: 1.8 Mb) to the almost 7,000 complete available today (collectively accounting for more than 300 Gb). PubMed abstracts

  4. The necessity of putting the actors into play However useful these compendia are, it is increasingly evident that in order to achieve a comprehensive view of the molecular basis of biological functions, we need to analyse the “actors” in the context of the “play” they are taking part of. Oltivai & Barabasi, Science298, 2002

  5. Proteins at the stage: Protein Interaction Networks Within any biological system, proteins seldom go out solo to perform their function; rather they assemble into permanent or transient macromolecular complexes, whose properties can be analysed at several levels of detail. • Protein B interacts with Protein D • >B|23..189 >D|899..947 • >B|SAR domain >D|907..919

  6. Proteins at the stage: Protein Interaction Networks Within any biological system, proteins seldom go out solo to perform their function; rather they assemble into permanent or transient macromolecular complexes, whose properties can be analysed at several levels of detail. • Protein B interacts with Protein D • >B|23..189 >D|899..947 • >B|SAR domain >D|907..919 • A interacts B, which interacts with A and D, which interacts C, which interacts with E and F, which interacts with A and G, which interacts with B and H, which interacts with C and I, which interacts with D and J...

  7. A B C D Proteins at the stage: Protein Interaction Networks Within any biological system, proteins seldom go out solo to perform their function; rather they assemble into permanent or transient macromolecular complexes, whose properties can be analysed at several levels of detail. • Protein B interacts with Protein D • >B|23..189 >D|899..947 • >B|SAR domain >D|907..919 • A interacts B, which interacts with A and D, which interacts C, which interacts with E and F, which interacts with A and G, which interacts with B and H, which interacts with C and I, which interacts with D and J...

  8. Structural bioinformatics, zoom lens to the cell Zoom in: from PINs to pathways to molecular interfaces Zoom out: from binary interactions to macromolecular assemblies to whole cells Aloy & Russell, FEBS Lett579, 2005

  9. Protein-protein interactions in the PDB The number of different interaction types has been estimated between 4000 and 10000. Garma et al., PLoS One7, 2012

  10. Protein-protein interactions in the PDB Two main flavors 1rfb | Interferon 2637 Å2 140 residues 2ybr | Tx - ScFv 915 Å2 61 residues 1bks | Trp synthase 1247 Å2 76 residues 1h26 | Cdk2/Cyclin/p53 1698 Å2 91 residues 598 Å2 28 residues 2ovq | Fbw7-Skp1-cyclin E 1721 Å2 81 residues 652 Å2 37 residues 1efu | Elongation factor 2236 Å2 162 residues

  11. PyMOL Demo Working with strucutures 2cci| Cdk2/Cyclin/CDC6

  12. Exercise Task 1: Elongin-pVH-HIF1A 1lm8 Task 2: RB-WASF2 1gux Task 3: SKP1-FBXW7-CCNE1 2ovq Task 4: Actin-DNAseI-WH2 2a40 Task 5: Dyenin 2pg1 Describe the interactions in terms of: - Buried surface area - How many residues are in contact - What kind of residues are involved (is there any bias?) Identify the players - Which domains are involved - Which one is the ELM class

  13. Protein-protein interactions in the PDB The number of different interaction types has been estimated between 4000 and 10000.

  14. 3D-ID Structures of protein-protein interactions The structural details of any protein interaction are, arguably, the most intimate knowledge about it we could ever get.

  15. Session 2b

  16. How many PPI types there are? Garma et al., PLoS One7, 2012

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