Conformation of the hypervariable region L3 without the key proline residue

Guarné, Alba; Bravo, Jerónimo; Calvo, Javier; Lozano, Francisco; Vives, Jordi; Fita, I.

doi:10.1002/pro.5560050121

Cited by 26 publications

(15 citation statements)

References 11 publications

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“…Table I shows the relationship between the conventional canonical structures in the κ CDR‐L3 and its key residues, which are important to consider when grafting CDRs onto a human antibody framework 6, 25–28. The κ CDR‐L3 currently assumed to have six canonical structures,8, 29–31 and the Type 1 canonical structures are the predominant among them. In the crystal structures from the PDB, the Type 1 canonical structures are the most abundant, too (see Supp.…”

Section: Resultsmentioning

confidence: 99%

Systematic classification of CDR‐L3 in antibodies: Implications of the light chain subtypes and the V_L–V_H interface

et al. 2009

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Antibody modeling is widely used for the analysis of antibody-antigen interactions and for the design of potent antibody drugs. The antibody combining site is composed of six complementarity determining regions (CDRs). The CDRs, except for CDR-H3, which is the most diverse CDR, form limited numbers of canonical structures, which can be identified from the amino acid sequences. A method to classify the CDR-H3 structure from its amino acid sequence was previously proposed. However, since those CDR structures were classified, many more antibody crystal structures have been determined. We performed systematic analyses of the CDR-L3 structures and found novel canonical structures, and we also classified a previously identified canonical structure into two subtypes. In addition, two differently defined canonical structures in the kappa and lambda subtypes were classified into the same canonical structure. We also identified a key residue in CDR-L3, which determines the conformation of CDR-H3. Several analyses of CDR-L3 loops longer than nine residues were performed. These new findings should be useful for structural modeling and are eventually expected to accelerate the design of antibody drugs.

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Section: Resultsmentioning

confidence: 99%

Systematic classification of CDR‐L3 in antibodies: Implications of the light chain subtypes and the V_L–V_H interface

et al. 2009

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“…This site is formed by six hypervariable loops known as complementarity determining regions (CDRs), three from the light (L1, L2, and L3), and three from the heavy (H1, H2, and H3) chain variable domains 2, 3. Despite the high sequence and length variability shown by CDRs, it has been found at the crystal structure level that, at least in five of them (L1, L2, L3, H1, and H2), the peptide backbone usually adopts a limited number of main chain conformations which have been called canonical structures 4–14. A particular canonical structure is defined by the length of the hypervariable loop and the residues present at key positions 5.…”

Section: Introductionmentioning

confidence: 99%

The CDR1 of the human λVI light chains adopts a new canonical structure

2005

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We performed a comparative analysis of the conformation of the CDR1 of the human λVI variable domains JTO and WIL and the equivalent loop of the λI light chains RHE and KOL, which are representative of the type I canonical structure for λ light chains. On the basis of the differences found in the main chain conformation, as well as the identity of the residues at key positions, we showed that the L1 of some λVI light chains adopts a conformation that represents a new type of canonical structure. The conformation of the L1 of those λVI light chains, is primarily determined by the presence of an Arg residue at position 25. The analysis of the λVI light chain sequences so far reported, showed that near 25% of those proteins have Gly at position 25 instead of Arg, which represents an allotypic variant of the λVI variable locus. The presence of Gly at position 25 in the L1 of λVI light chains would imply a different conformation for this loop. Additionally, the position 68 in λVI light chains, which is at the top of the FR3 loop, showed such spatial orientation and variability that suggested its participation in the conformation of the antigen recognition surface in this subgroup of λ chains. Proteins 2006. © 2005 Wiley‐Liss, Inc.

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“…This is due to a codon loss when the V L and J gene segments were joined during somatic recombination. Although there is no accepted canonical classification to describe the CDR‐L3 structure of 5a19, its conformation is the same as that observed in the anti‐CD25 mAb CRIS [17] and the catalytic antibody 17E8 [18]. CDR‐H3 is seven residues in length and is thus slightly shorter than the mean length of 8.7 residues noted by Wu et al [19].…”

Section: Resultsmentioning

confidence: 75%

Structural and functional characterization of a monoclonal antibody specific for the preS1 region of hepatitis B virus

et al. 2001

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The monoclonal antibody 5a19, raised against the ay serotype of hepatitis B virus, binds to the segment of the preS1 region comprising residues 37^43, which is implicated in attachment of the virus to hepatocytes. The dissociation constant, derived from kinetic studies using surface plasmon resonance techniques, is in the low nanomolar range. The nucleotide sequence of the variable domains has been determined and the corresponding germ-line genes have been identified. The three-dimensional structure of the Fab fragment has been determined by X-ray crystallography to 2.6 A î resolution. ß

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Conformation of the hypervariable region L3 without the key proline residue

Cited by 26 publications

References 11 publications

Systematic classification of CDR‐L3 in antibodies: Implications of the light chain subtypes and the V_L–V_H interface

Systematic classification of CDR‐L3 in antibodies: Implications of the light chain subtypes and the V_L–V_H interface

The CDR1 of the human λVI light chains adopts a new canonical structure

Structural and functional characterization of a monoclonal antibody specific for the preS1 region of hepatitis B virus

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Conformation of the hypervariable region L3 without the key proline residue

Cited by 26 publications

References 11 publications

Systematic classification of CDR‐L3 in antibodies: Implications of the light chain subtypes and the VL–VH interface

Systematic classification of CDR‐L3 in antibodies: Implications of the light chain subtypes and the VL–VH interface

The CDR1 of the human λVI light chains adopts a new canonical structure

Structural and functional characterization of a monoclonal antibody specific for the preS1 region of hepatitis B virus

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Systematic classification of CDR‐L3 in antibodies: Implications of the light chain subtypes and the V_L–V_H interface

Systematic classification of CDR‐L3 in antibodies: Implications of the light chain subtypes and the V_L–V_H interface