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Modularity as an Organizing Principle in Protein Structure
Unequal recombination drives the repetition of structural elements
Titin
x 300
Core of an average domain
~150 AA
20 different amino acids –> 20150 = 10195 different sequences
Of these ~1038 are expected to have different fold
(i.e. less than 20% sequence identity)
Estimated number of naturally occurring folds ~1000
Fraction of theoretically possible “folds” used in nature
~ 1/1034 = 0.00000000000000000000000000000001%
Super secondary Structure elements
Unequal recombination drives the repetition of structural elements
Titin
x 300
TIM barrel
muramidase
Structures with
alpha-hairpin motifs
beta-hairpin
Motifs
beta-alpha-beta
Motif
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Proteins with more than 30% AA identity
almost always adopt the same fold.
Stability -Gfolding
Proteins as “Islands of Stability” in Sequence Space
folded
unfolded
Sequence
Bridges in between islands
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Cordes et al. Nat. Struct. Biol 2000 Dec;7(12):1129-32.
QuickTime™ and a
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QuickTime™ and a
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QuickTime™ and a
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are needed to see this picture.
Glykos, N.M., Cesareni, G. & Kokkinidis, M. (1999), Structure 7, 597-603
Paracelsus Challenge
< 50% of AA
changed
B1 domain of protein G
Janus