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Abstract
Proteins display a hierarchy of structural features at primary, secondary, tertiary,
and higher-order levels, an organization that guides our current understanding of
their biological properties and evolutionary origins. Here, we reveal a structural
organization distinct from this traditional hierarchy by statistical analysis of correlated
evolution between amino acids. Applied to the S1A serine proteases, the analysis indicates
a decomposition of the protein into three quasi-independent groups of correlated amino
acids that we term "protein sectors." Each sector is physically connected in the tertiary
structure, has a distinct functional role, and constitutes an independent mode of
sequence divergence in the protein family. Functionally relevant sectors are evident
in other protein families as well, suggesting that they may be general features of
proteins. We propose that sectors represent a structural organization of proteins
that reflects their evolutionary histories.