Hypervariability

Chothia C, A M Lesk, A Tramontano, M Levitt, S Smith-Gill, G Air, S Sheriff, E A Padlan and D Davies 1989. Conformations of Immunoglobulin Hypervariable Regions. Nature 342 877-883. 

C Chothia, AM Lesk. Canonical structures for the hypervariable regions of immunoglobulins. J Mol Biol 196 901-917, 1987. 

RM Fine, H Wang, PS Shenkm, DL Yarmush, C Levmthal. Predicting antibody hypervariable loop conformations. II Minimization and molecular dynamics studies of MCP603 from many randomly generated loop conformations. Proteins 1 342-362, 1986. 

ACR Martin, JC Cheetham, AR Rees. Modeling antibody hypervariable loops A combined algorithm. Proc Natl Acad Sci USA 86 9268-9272, 1989. 

The antigen-binding site is formed by close association of the hypervariable regions from both heavy and light chains... 

Figure 15.12 Schematic diagram of the barrel arrangement of four p strands from each of the variable domains in Fab. The six hypervariable regions, CDR1-CDR3 from the light chain (L1-L3) and from the heavy chain (H1-H3), are at one end of this barrel. (From J. Novotny et al., /. Biol. Chem. 2S8 14433-14437, 1983.)...

Figure 15.13 (a) Drawing of a space-filiing model of the hypervariable regions of an Fab fragment. The superpositions of five sections are shown, cut through a model as shown in (b). It is clearly seen that all six hypervariable regions (L1-L3, H1-H3) contribute to the surface shown here. (From C. Chothia and A. Lesk, /. Mol. Biol. 196 901-917, 1987.)... 

T-cell receptors have variable and constant immunoglobulin domains and hypervariable regions... 

The constant domain has a stable framework structure composed of two antiparallel sheets comprising seven p strands, four in one sheet and three in the other. The variable domains have a similar framework structure but comprising nine p strands, five in one sheet and four in the other. The three hypervariable regions are in loops at one end of the variable domain. The variable domains from the heavy and light chains associate through their five-stranded p sheets to form a barrel with the hypervariable loop regions from both domains close together at the top of the barrel. 

Bruccoleri, R.E., Haber, E., Novotny, J. 5tructure of antibody hypervariable loops reproduced by a conformational search algorithm. Nature 335 564-568, 1988. 

Chothia, C., et al. Conformations of immunoglobulin hypervariable regions. Nature 343 877-883, 1989. 

The hypervariable regions are clustered in loop regions at one end of the variable domain 30S... 

The four hypervariable regions are indicated by the bars. The constant regions in this disanalog family include a 50 AA N-terminal region (not shown) and the 6 cysteine residues. 

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