The distortions related to proline in a alpha-helix can be accommodated by different structural elements. To obtain an exhaustive view of these distortions, we data mined a non-redundant subset of the Protein Data Bank in search of proline residues included either within contiguous helices or within structural motifs in which two helices are joined by a few linker residues with backbone dihedral angles in the generous alpha region. The distortions correspond to "typical" and "non-typical" proline distortions, with relative ratio of 0.65 and 0.35, respectively. Analysis of "non-typical" proline distortions indicates that most linkers have one (75%) or two residues (20%) and that proline is preferentially located at the second or third position of the second helix (95%). The dihedral angles of the linker residues are located in two areas of the generous alpha region. Structures with linker(s) in the alpha 1 area, which is characterized by very negative phi values, possess i to 1-5 H-bonds and correspond to pi bulges. Structures with linker(s) in the alpha 2 area, which links the alpha and beta regions, possess i to i-3 H-bonds and correspond to tight turns. Further classification of bulges and turns as a function of the linker length and proline position yields five canonical structures, representing 85% of "non-typical" proline distortions. These structures are characterized by distinct H-bonding patterns and structural determinants and correspond to different classes of pi bulges and tight turns. This hierarchical approach provides a straightforward and robust classification of proline-related helical distortions. (C) 2010 Elsevier Inc. All rights reserved.