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Modularity as an Organizing Principle in Protein Structure. Unequal recombination drives the repetition of structural elements. Titin. x 300. TIM barrel. muramidase. Core of an average domain ~150 AA. 20 different amino acids –> 20 150 = 10 200 different sequences.
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Unequal recombination drives the repetition of structural elements Titin x 300 TIM barrel muramidase
Core of an average domain ~150 AA 20 different amino acids –> 20150 = 10200different sequences Of these ~1038are 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%
Structures with alpha-hairpin motifs
beta-hairpin Motifs
beta-alpha-beta Motif
Proteins with more than 30% AA identity almost always adopt the same fold.
Proteins as “Islands of Stability” in Sequence Space folded Stability -Gfolding unfolded Sequence
Bridges in between islands Cordes et al. Nat. Struct. Biol 2000 Dec;7(12):1129-32.
Glykos, N.M., Cesareni, G. & Kokkinidis, M. (1999), Structure 7, 597-603
Paracelsus Challenge < 50% of AA changed B1 domain of protein G Janus