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Framework 1 CDR 1 Framework 2 CDR 2 Framework 3a Framework 3b CDR 3 Framework 4

Residues1-27

The first gap to be placed concerns the one amino acid insertions in the VL kappa framework 1 compared to VL lambda and VH. Kabat placed this insertion/deletion at the 10th residue from the amino terminus. However, as a superposition of representative lambda and kappa chain structures shows, the amide nitrogen of the 7th residue assumes a structurally equivalent position in Vl and Vk chains, while the C=O oxygen of the 7th residue of Vl is structurally equivalent to the C=O oxygen of the 8th residue in Vk. Structurally, the gap in Vl relative to Vk should therefore be placed either in position L7 or L8 (Spada et al., 1998).

The corresponding segment of TCR Vb chains is VL kappa-like in length and structure, including the very frequent occurrence of a cis-proline in position B8, while some Va-chains are Vk-like and others resemble Vl with its one-residue deletion. For Vg and Vd there is not enough structural information available yet, although the single delta chain for which a structure has been solved (Li et al., 1998, PDB entry 1TVD) is Vk-like in length.

( update Info on Vg, / Vd )

Framework Region 1

Click on the Pictures to get an annotated close-up view on the "kink"

VH domains, while corresponding in length to Vl, show a larger structural variation in this region (Langedijk et al., 1998, Jung et al. 2001, Honegger & Plückthun, 2001), and the gap could equally well be placed in position H7, H8 or H9. We therefore chose to place the gap in position H8. The conserved cysteine residue forming the intradomain disulfide bridge therefore always carries the label "23" as in the IMGT numbering scheme, while according to Kabat, it was labeled L23 in Vk and Vl, H22 in VH, 23 in TCR Va and Vb and 21 in TCR Vg and Vd. 

AAAAA Homepage Zürich University Dept. of Biochemistry Plückthun Group Annemarie Honegger

Last Modified by A.Honegger Friday, January 28, 2005