Protein Crystallography Clickable Map

Molecular Replacement Using Known Structures

Huub Driessen and Ian Tickle

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Why is it that once the protein structure of one member of a family has been solved ab initio, it is easier to solve more members of the same family? Compare the structures of two members of the crystallin family which have 90% sequence identity.

The biggest sequence difference is a deletion of 1 residue (residue 86 in red) in the linker connecting the two domains in (at the bottom of the molecule in the display) ­D Crystallin compared to ­B Crystallin. A structural difference is that the C-terminal tails have a different conformation. Yet, it is clear that the three-dimensional structures of both proteins are at first sight indistinguishable. Proteins have similar three-dimensional conformations for sequence identities as low as 20%. This phenomenon is at the basis of molecular replacement.

The principle of molecular replacement

When identical or similar structures exist in different crystallographic environments, similarities between their diffraction patterns, which are direcly related to their Fourier transforms, would be expected. The technique of Molecular Replacement exploits this similarity to determine phases. The dominant application is

Examine the film to see how the rotation and translation steps relate the model x1 (e.g. ­B Crystallin of which the structure was known) and the target x2 (e.g. ­D Crystallin before that its structure was known).

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