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Modularity as an Organizing Principle in Protein Structure

Unequal recombination drives the repetition of structural elements like Titin x 300 TIM barrel muramidase core of an average domain (~150 AA). There are estimated to be 20 different amino acids with a potential of 20150 combinations, resulting in 10200 unique sequences. A vast majority (~1038) are expected to have different folds, showcasing the diversity in protein structures. The estimated number of naturally occurring folds is around 1000, indicating the richness of protein structure space. Structural elements like alpha-hairpin motifs, beta-hairpin motifs, and beta-alpha-beta motifs play crucial roles in determining protein folds. Proteins with more than 30% amino acid identity usually adopt the same fold, presenting as "islands of stability" in sequence space. This study emphasizes the significance of modularity and stability in protein folding, bridging the gap between sequence variability and structural integrity.

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Modularity as an Organizing Principle in Protein Structure

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  1. Modularity as an Organizing Principle in Protein Structure

  2. Unequal recombination drives the repetition of structural elements Titin x 300 TIM barrel muramidase

  3. 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%

  4. Super secondary Structure elements

  5. Structures with alpha-hairpin motifs

  6. beta-hairpin Motifs

  7. beta-alpha-beta Motif

  8. Proteins with more than 30% AA identity almost always adopt the same fold.

  9. Proteins as “Islands of Stability” in Sequence Space folded Stability -Gfolding unfolded Sequence

  10. Bridges in between islands Cordes et al. Nat. Struct. Biol 2000 Dec;7(12):1129-32.

  11. Glykos, N.M., Cesareni, G. & Kokkinidis, M. (1999), Structure 7, 597-603

  12. Paracelsus Challenge < 50% of AA changed B1 domain of protein G Janus

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