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

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Presentation on theme: "Structures of protein-protein interactions: zoom lens to the cell Ricardo C. Rodríguez de la Vega Universit é Paris-Sud Orsay, France."— Presentation transcript:

1 Structures of protein-protein interactions: zoom lens to the cell Ricardo C. Rodríguez de la Vega Universit é 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, Science 298, 2002

5 Protein B interacts with Protein D >B| >D| >B|SAR domain>D| 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. Proteins at the stage: Protein Interaction Networks

6 Protein B interacts with Protein D >B| >D| >B|SAR domain>D| 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... 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.

7 Protein B interacts with Protein D >B| >D| >B|SAR domain>D| 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... 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. A B C D

8 Aloy & Russell, FEBS Lett 579, 2005 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

9 Protein-protein interactions in the PDB The number of different interaction types has been estimated between 4000 and Garma et al., PLoS One 7, 2012

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

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

12 Exercise Task 1: Elongin-pVH-HIF1A1lm8 Task 2: RB-WASF21gux Task 3: SKP1-FBXW7-CCNE12ovq Task 4: Actin-DNAseI-WH22a40 Task 5: Dyenin2pg1 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

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

15 Session 2b

16 How many PPI types there are? Garma et al., PLoS One 7, 2012


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