Specific antibody - DNA interaction: A novel strategy for fight dna recognition
Anti-double-stranded DNA monoclonal antibodies against a viral transcriptional regulatory site are capable of discriminating single-base replacements with affinities of 1 × 10-9 M, which were optimized for the length of the duplex used as the immunogen. Their affinity for DNA duplexes of increasing...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Publicado: |
2003
|
| Materias: | |
| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v42_n20_p6218_DiPietro http://hdl.handle.net/20.500.12110/paper_00062960_v42_n20_p6218_DiPietro |
| Aporte de: |
| id |
paper:paper_00062960_v42_n20_p6218_DiPietro |
|---|---|
| record_format |
dspace |
| spelling |
paper:paper_00062960_v42_n20_p6218_DiPietro2023-06-08T14:30:39Z Specific antibody - DNA interaction: A novel strategy for fight dna recognition Cerutti, María Laura Ferreiro, Diego U. Alonso, Leonardo de Prat Gay, Gonzalo DNA Genes Interfaces (materials) Molecules Specific heat Structural analysis Monoclonal antibodies Antibodies antigen DNA DNA antibody DNA base DNA fragment double stranded DNA monoclonal antibody protein water antigen recognition article binding affinity binding kinetics binding site conformational transition diffusion DNA denaturation DNA sequence electricity energy heat molecular stability nonhuman nucleic acid base substitution priority journal protein DNA interaction solute spectroscopy structure analysis thermodynamics transcription regulation Animals Antibodies, Antinuclear Antibodies, Monoclonal Antigen-Antibody Reactions Base Sequence Binding Sites DNA DNA, Viral DNA-Binding Proteins Kinetics Molecular Sequence Data Nucleic Acid Conformation Oncogene Proteins, Viral Papillomaviridae Thermodynamics Anti-double-stranded DNA monoclonal antibodies against a viral transcriptional regulatory site are capable of discriminating single-base replacements with affinities of 1 × 10-9 M, which were optimized for the length of the duplex used as the immunogen. Their affinity for DNA duplexes of increasing length is lower, but reaches a plateau at 2 × 10-8 M, still a fairly high affinity compared to those of most known natural anti-DNA antibodies. The ability of the antibodies to bind to a 166 bp DNA fragment containing the specific sequence strongly suggests that these have the potential of binding the specific sequence within larger genomic DNA fragments. Electrostatic interactions do not play a significant role, the opposite of what is observed in natural DNA binding interfaces. In addition, the insensitivity of the antibody - DNA interaction to solute effects is indicative of a marginal participation of water molecules at the interface compared to the level of participation at the natural E2 - DNA interface. Spectroscopic evidence of base unstacking strongly suggests substantial denaturation of antibody-bound DNA, in agreement with thermodynamic results that show an unusual positive heat capacity change, which could be explained at least in part by the exposure of DNA bases upon binding. Lower local DNA stability cooperates with sequence recognition in producing the highest binding affinity. A slow rate of antibody-DNA association indicates an energy barrier imposed by conformational rearrangements, as opposed to an electrostatically assisted diffusion-controlled collision in the E2 DNA binding domain. While the E2 - DNA interaction takes place through a typical direct readout mechanism, the anti-double-stranded DNA monoclonal antibody - DNA interaction could be viewed as a distinctive case of indirect readout with a significant distortion in the DNA conformation. However, the precise mechanism with which the DNA bases are accommodated in the antibody combining site will require structural analysis at atomic resolution. These results constitute a first stage for unveiling the unusual molecular recognition mechanism of a specific DNA sequence by antibodies. This mechanism could represent the strategy with which the immune system tightly and specifically recognizes a DNA antigen. Fil:Cerutti, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ferreiro, D.U. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Alonso, L.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:De Prat-Gay, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v42_n20_p6218_DiPietro http://hdl.handle.net/20.500.12110/paper_00062960_v42_n20_p6218_DiPietro |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
DNA Genes Interfaces (materials) Molecules Specific heat Structural analysis Monoclonal antibodies Antibodies antigen DNA DNA antibody DNA base DNA fragment double stranded DNA monoclonal antibody protein water antigen recognition article binding affinity binding kinetics binding site conformational transition diffusion DNA denaturation DNA sequence electricity energy heat molecular stability nonhuman nucleic acid base substitution priority journal protein DNA interaction solute spectroscopy structure analysis thermodynamics transcription regulation Animals Antibodies, Antinuclear Antibodies, Monoclonal Antigen-Antibody Reactions Base Sequence Binding Sites DNA DNA, Viral DNA-Binding Proteins Kinetics Molecular Sequence Data Nucleic Acid Conformation Oncogene Proteins, Viral Papillomaviridae Thermodynamics |
| spellingShingle |
DNA Genes Interfaces (materials) Molecules Specific heat Structural analysis Monoclonal antibodies Antibodies antigen DNA DNA antibody DNA base DNA fragment double stranded DNA monoclonal antibody protein water antigen recognition article binding affinity binding kinetics binding site conformational transition diffusion DNA denaturation DNA sequence electricity energy heat molecular stability nonhuman nucleic acid base substitution priority journal protein DNA interaction solute spectroscopy structure analysis thermodynamics transcription regulation Animals Antibodies, Antinuclear Antibodies, Monoclonal Antigen-Antibody Reactions Base Sequence Binding Sites DNA DNA, Viral DNA-Binding Proteins Kinetics Molecular Sequence Data Nucleic Acid Conformation Oncogene Proteins, Viral Papillomaviridae Thermodynamics Cerutti, María Laura Ferreiro, Diego U. Alonso, Leonardo de Prat Gay, Gonzalo Specific antibody - DNA interaction: A novel strategy for fight dna recognition |
| topic_facet |
DNA Genes Interfaces (materials) Molecules Specific heat Structural analysis Monoclonal antibodies Antibodies antigen DNA DNA antibody DNA base DNA fragment double stranded DNA monoclonal antibody protein water antigen recognition article binding affinity binding kinetics binding site conformational transition diffusion DNA denaturation DNA sequence electricity energy heat molecular stability nonhuman nucleic acid base substitution priority journal protein DNA interaction solute spectroscopy structure analysis thermodynamics transcription regulation Animals Antibodies, Antinuclear Antibodies, Monoclonal Antigen-Antibody Reactions Base Sequence Binding Sites DNA DNA, Viral DNA-Binding Proteins Kinetics Molecular Sequence Data Nucleic Acid Conformation Oncogene Proteins, Viral Papillomaviridae Thermodynamics |
| description |
Anti-double-stranded DNA monoclonal antibodies against a viral transcriptional regulatory site are capable of discriminating single-base replacements with affinities of 1 × 10-9 M, which were optimized for the length of the duplex used as the immunogen. Their affinity for DNA duplexes of increasing length is lower, but reaches a plateau at 2 × 10-8 M, still a fairly high affinity compared to those of most known natural anti-DNA antibodies. The ability of the antibodies to bind to a 166 bp DNA fragment containing the specific sequence strongly suggests that these have the potential of binding the specific sequence within larger genomic DNA fragments. Electrostatic interactions do not play a significant role, the opposite of what is observed in natural DNA binding interfaces. In addition, the insensitivity of the antibody - DNA interaction to solute effects is indicative of a marginal participation of water molecules at the interface compared to the level of participation at the natural E2 - DNA interface. Spectroscopic evidence of base unstacking strongly suggests substantial denaturation of antibody-bound DNA, in agreement with thermodynamic results that show an unusual positive heat capacity change, which could be explained at least in part by the exposure of DNA bases upon binding. Lower local DNA stability cooperates with sequence recognition in producing the highest binding affinity. A slow rate of antibody-DNA association indicates an energy barrier imposed by conformational rearrangements, as opposed to an electrostatically assisted diffusion-controlled collision in the E2 DNA binding domain. While the E2 - DNA interaction takes place through a typical direct readout mechanism, the anti-double-stranded DNA monoclonal antibody - DNA interaction could be viewed as a distinctive case of indirect readout with a significant distortion in the DNA conformation. However, the precise mechanism with which the DNA bases are accommodated in the antibody combining site will require structural analysis at atomic resolution. These results constitute a first stage for unveiling the unusual molecular recognition mechanism of a specific DNA sequence by antibodies. This mechanism could represent the strategy with which the immune system tightly and specifically recognizes a DNA antigen. |
| author |
Cerutti, María Laura Ferreiro, Diego U. Alonso, Leonardo de Prat Gay, Gonzalo |
| author_facet |
Cerutti, María Laura Ferreiro, Diego U. Alonso, Leonardo de Prat Gay, Gonzalo |
| author_sort |
Cerutti, María Laura |
| title |
Specific antibody - DNA interaction: A novel strategy for fight dna recognition |
| title_short |
Specific antibody - DNA interaction: A novel strategy for fight dna recognition |
| title_full |
Specific antibody - DNA interaction: A novel strategy for fight dna recognition |
| title_fullStr |
Specific antibody - DNA interaction: A novel strategy for fight dna recognition |
| title_full_unstemmed |
Specific antibody - DNA interaction: A novel strategy for fight dna recognition |
| title_sort |
specific antibody - dna interaction: a novel strategy for fight dna recognition |
| publishDate |
2003 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v42_n20_p6218_DiPietro http://hdl.handle.net/20.500.12110/paper_00062960_v42_n20_p6218_DiPietro |
| work_keys_str_mv |
AT ceruttimarialaura specificantibodydnainteractionanovelstrategyforfightdnarecognition AT ferreirodiegou specificantibodydnainteractionanovelstrategyforfightdnarecognition AT alonsoleonardo specificantibodydnainteractionanovelstrategyforfightdnarecognition AT depratgaygonzalo specificantibodydnainteractionanovelstrategyforfightdnarecognition |
| _version_ |
1768542296035295232 |