Journal: Protein Engineering, Design and Selection
Article Title: Adaption of human antibody λ and κ light chain architectures to CDR repertoires
doi: 10.1093/protein/gzz012
Figure Lengend Snippet: Structural differences between V L κ and V L λ were determined by RandomForest. (A) The most reliable classifiers for assigning the dataset of full light chain structures to the κ and λ isotypes are identified by the mean decrease gini (variables defined in ). (B) Unknown sequences can be reliably assigned to the κ and λ isotype according to the length of LFR4. (C) An overlay of representative Cα-traces displays how the exclusion (V L κ, green, 5ifa ( Huang et al ., 2004 )) or incorporation (V L λ, red, 3ujj ( Guan et al ., 2013 )) of L106A in LFR4 affects the structure. (D) V L λ structures exhibited a significantly lower energy penalty for peptide bonds in the cis-conformation if compared to V L κ structures. (E) The number of residues in LFR1 enables to distinguish between V L κ and V L λ sequences. (F) Representative structures of V L λ (3ujj ( Gorny et al ., 2011 ), red) and V L κ (5ifa ( Jardine et al ., 2016 ), green) illustrate structural differences in LFR1. V L κ structures frequently contain a cis-proline at position L8, stabilizing a fold that dramatically differs from V L λ structures that favor trans-prolines at positions L7 and L8. (G) ‘ Sequence logo’ representation of the amino acids identities in LFR1 of V L κ (top) and V L λ (bottom). (H, I) Representative structures of V L κ (H , green, PDBs: 3drq ( Julien et al ., 2008 ), 4ygv ( Schiele et al ., 2015 ), 4jm4 ( Kong et al ., 2013 ) and 4zyk ( Gilman et al ., 2015 )) and V L λ ( I , red, PDBs: 4h8w ( Acharya et al ., 2014 ), 1aqk ( Faber et al ., 1998 ), 5d7s ( Eylenstein et al ., 2016 ), 5cck ( Lee et al ., 2015 )) clearly differ in the conserved environment of residue L95. Yellow cylinders, hydrogen bonds; yellow and orange structure, heavy chain; cyan residue, Gln L90; magenta, Pro L95; orange, Thr L97; blue, Phe L98; green, Val L97. (J) ‘ Sequence logo’ representation of the amino acids occurrence spatially neighboring residues of L95 in V L κ (top) and V L λ (bottom).
Article Snippet: R-studio was used to perform the RandomForest analyses (randomForest R-package version 4.6-14) ( ).
Techniques: Sequencing, Residue
