Globin fold

The globin fold is a common three-dimensional fold in proteins. This fold typically consists of eightVerify source|date=October 2007 alpha helices, although some proteins have additional helix extensions at their termini. The globin fold is found in its namesake proteins hemoglobin and myoglobin as well as in phycocyanin proteins. Because myoglobin was the first protein whose structure was solved, the globin fold was thus the first protein fold discovered. Since the globin fold contains only helices, it is classified as an all-alpha protein fold.

Helix packing

The eight helices of the globin fold core share significant nonlocal structure, unlike other structural motifs in which amino acids close to each other in primary sequence are also close in space. The helices pack together at an average angle of about 50 degrees, significantly steeper than other helical packings such as the helix bundle. The exact angle of helix packing depends on the sequence of the protein, because packing is mediated by the sterics and hydrophobic interactions of the amino acid side chains near the helix interfaces.

equence conservation

Although the globin fold is highly evolutionarily conserved, the sequences that form the fold can have as low as 16% sequence identity. While the sequence specificity of the fold is not stringent, the hydrophobic core of the protein must be maintained and hydrophobic patches on the generally hydrophilic solvent-exposed surface must be avoided in order for the structure to remain stable and soluble. The most famous mutation in the globin fold is a change from glutamate to valine in one chain of the hemoglobin molecule. This mutation creates a "hydrophobic patch" on the protein surface that promotes intermolecular aggregation, the molecular event that gives rise to sickle-cell anemia.

References

* Branden C, Tooze J. (1999). "Introduction to Protein Structure" 2nd ed. Garland Publishing: New York, NY.

External links

* [http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.b.b.html SCOP globin folds]