This exercise is a part of RCSB PDB Curriculum Module Biomolecular Structures and Models and was developed as part of the RCSB Collaborative Curriculum Development Program 2015.

Exploring a Protein Structure in the RCSB PDB: Insulin

Learning Goals:

  1. Visualize the structure of a given molecule using RCSB PDB resources.
  2. Explore the structure to understand its structure function relationships

Exercise:

Review the Molecule of the Month feature on Insulin for background information. What are the main ideas of this feature?

Note that there are a few PDB entries listed throughout the feature. For example, PDB entry 4ins can be linked from

Open the Structure Summary page for the PDB entry 4ins (http://www.rcsb.org/pdb/explore/explore.do?structureId=4ins).

Read/review the page and answer the following questions based on the descriptions provided:

  1. What is the source (organism) of the insulin molecule in this structure?

  2. Name the authors who solved the structure of this protein?

  3. Explore the 3-D structure of this protein by clicking on JSmol (hyperlink) under the image as seen below:

    4. View the polymer chains shown to contain helical ribbons (in magenta), arrows (in golden yellow) and coil-like regions (white/grey).

    Mouse-over the small grey atom (highlighted by a red arrow, in the figure below). What is it and why do you see this atom in the insulin structure (Hint: read the title and abstract of the structure for clues)

  4. Change the viewer to PV

    5. The default view is colored by chain (i.e. each protein (polymer) chain in the structure is colored in a different color.

    Based on the 3-D model that you see here describe the overall composition of insulin – how many and what chains are present in the structure. Also describe the structure of each insulin molecule in terms of the helical, arrow-like or coiled regions in each chain.

  5. Go back to the JSmol view of the PDB entry.

    6. In the various options click on the box next to S-S bonds to show the disulfide bonds in the structure.

    Note yellow SS bond lines appear in the model. These bonds are formed by oxidation of two specific sulfur-containing amino acids. How many such bonds do you see?

  6. Are these S-S bonds within the same polymer chain or between different chains of insulin? (Hint: Color the ribbons by sequence to see if the S-S bonding is between the same or different polymer chains).

  7. What do you think is the role of these S-S bonds? Describe in 1-2 sentences.