Protein Architecture

Exercises and Demonstrations

Aidan Budd

Quarternary Protein Structure

Domain-Domain interactions

Demonstration

Human haemoglobin 1DXT - domain-domain interactions between two beta and two alpha chains

PyMOL session file (with beta chains in green, alpha in red)
Link to PDBe Record: 1DXT
Link to PDBsum: 1DXT
Original PDB file to download

Globular Domains and Linear Motifs

Side-chain specificity of a motif-binding groove in a globular domain

Demonstration

The FxDxF motif of Amphiphysin binding to the AP-2 Clathrin Adaptor Alpha-Appendage - the surface of a domain provides a very specific binding groove for the motif, in particular providing a close-fit for one of the phenyalanine side-chains

PyMOL session file (motif side-on, with a transparent domain surface, secondary structure cartoons coloured by type of secondary structure element)
PyMOL session file (close up of motif with sidechains showing against surface of the domain)
Link to ELM resource for FxDxF motif - LIG_AP2alpha_1
Link to PDBe Record: 1KY7
Link to PDBsum: 1KY7
Original PDB file to download

Different dynamics/flexibility of peptide compared to globular domain

Demonstration

Phosphothreonine peptide binding to the FHA1 domain of Rad53 solved using NMR, 20 different states provided in the PDB record. Quickly displaying the 20 states after one another provides an impression of the much greater mobility/dynamism of the peptide compared to the globular domain.

PyMOL session file (cartoon view, phosphothreonine shown with sticks)
Link to ELM resourece for FHA1-binding motif - LIG_FHA_1
Link to PDBe Record: 1K3Q
Link to PDBsum: 1K3Q
Original PDB file to download

Conservation of strongly-constrained motif sidechains

Demonstration

MAD1 has been shown to interact with MAD2 via an MAD2-binding motif in MAD1. The 3D structure has been solved for this complex, and the motif shows strong conservation of the regular expression used to describe the binding peptide in the ELM resource, including humans, yeast, and slime mold.

Link to ELM resource for MAD2 binding motif - LIG_MAD2 (regular expression: [KR][IV][LV].....P)
Link to UniProt record for MAD1 (MD1L1_HUMAN, Q9Y6D9), containing an instance of the LIG_MAD2 motif whose structure has been determined (KVLHMSLNP)
Link to PDBe Record for MAD1-structure: 1g04
TreeFam family record for the family TF101083

previously-downloaded full alignment (CLUSTAL format)

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