2q76 › Citations

Affinity maturation increases the stability and plasticity of the Fv domain of anti-protein antibodies.

Acierno JP, Braden BC, Klinke S, Goldbaum FA, Cauerhff A
J Mol Biol 374 130-46 (2007)
Cited: 26 times
EuropePMC logo PMID: 17916365

Abstract

The somatic mutations accumulated in variable and framework regions of antibodies produce structural changes that increase the affinity towards the antigen. This implies conformational and non covalent bonding changes at the paratope, as well as possible quaternary structure changes and rearrangements at the V(H)-V(L) interface. The consequences of the affinity maturation on the stability of the Fv domain were studied in a system composed of two closely related antibodies, F10.6.6 and D44.1, which recognize the same hen egg-white lysozyme (HEL) epitope. The mAb F10.6.6 has an affinity constant 700 times higher than D44.1, due to a higher surface complementarity to HEL. The structure of the free form of the Fab F10.6.6 presented here allows a comparative study of the conformational changes produced upon binding to antigen. By means of structural comparison, kinetics and thermodynamics of binding and stability studies on Fab and Fv fragments of both antibodies, we have determined that the affinity maturation process of anti-protein antibodies affects the shape of the combining site and the secondary structure content of the variable domain, stabilizes the V(H)-V(L) interaction, and consequently produces an increase of the Fv domain stability, improving the binding to antigen.

Articles - 2q76 mentioned but not cited (9)

  1. Blind prediction performance of RosettaAntibody 3.0: grafting, relaxation, kinematic loop modeling, and full CDR optimization. Weitzner BD, Kuroda D, Marze N, Xu J, Gray JJ. Proteins 82 1611-1623 (2014)
  2. Optimizing antibody affinity and stability by the automated design of the variable light-heavy chain interfaces. Warszawski S, Borenstein Katz A, Lipsh R, Khmelnitsky L, Ben Nissan G, Javitt G, Dym O, Unger T, Knop O, Albeck S, Diskin R, Fass D, Sharon M, Fleishman SJ. PLoS Comput Biol 15 e1007207 (2019)
  3. Multi-constraint computational design suggests that native sequences of germline antibody H3 loops are nearly optimal for conformational flexibility. Babor M, Kortemme T. Proteins 75 846-858 (2009)
  4. Local and Global Rigidification Upon Antibody Affinity Maturation. Fernández-Quintero ML, Loeffler JR, Bacher LM, Waibl F, Seidler CA, Liedl KR. Front Mol Biosci 7 182 (2020)
  5. Structure-based cross-docking analysis of antibody-antigen interactions. Kilambi KP, Gray JJ. Sci Rep 7 8145 (2017)
  6. Conformational selection of allergen-antibody complexes-surface plasticity of paratopes and epitopes. Fernández-Quintero ML, Loeffler JR, Waibl F, Kamenik AS, Hofer F, Liedl KR. Protein Eng Des Sel 32 513-523 (2019)
  7. Surprisingly Fast Interface and Elbow Angle Dynamics of Antigen-Binding Fragments. Fernández-Quintero ML, Kroell KB, Heiss MC, Loeffler JR, Quoika PK, Waibl F, Bujotzek A, Moessner E, Georges G, Liedl KR. Front Mol Biosci 7 609088 (2020)
  8. Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing. Valdés-Alemán J, Téllez-Sosa J, Ovilla-Muñoz M, Godoy-Lozano E, Velázquez-Ramírez D, Valdovinos-Torres H, Gómez-Barreto RE, Martinez-Barnetche J. MAbs 6 493-501 (2014)
  9. A New in Silico Antibody Similarity Measure Both Identifies Large Sets of Epitope Binders with Distinct CDRs and Accurately Predicts Off-Target Reactivity. Musnier A, Bourquard T, Vallet A, Mathias L, Bruneau G, Ayoub MA, Travert O, Corde Y, Gallay N, Boulo T, Cortes S, Watier H, Crépieux P, Reiter E, Poupon A. Int J Mol Sci 23 9765 (2022)


Reviews citing this publication (5)

  1. Computer-aided antibody design. Kuroda D, Shirai H, Jacobson MP, Nakamura H. Protein Eng Des Sel 25 507-521 (2012)
  2. Survey of the year 2007 commercial optical biosensor literature. Rich RL, Myszka DG. J Mol Recognit 21 355-400 (2008)
  3. Breaking the law: unconventional strategies for antibody diversification. Kanyavuz A, Marey-Jarossay A, Lacroix-Desmazes S, Dimitrov JD. Nat Rev Immunol 19 355-368 (2019)
  4. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions. Akiba H, Tsumoto K. J Biochem 158 1-13 (2015)
  5. Generation of recombinant antibodies and means for increasing their affinity. Altshuler EP, Serebryanaya DV, Katrukha AG. Biochemistry (Mosc) 75 1584-1605 (2010)

Articles citing this publication (12)

  1. Antibody recognition of a unique tumor-specific glycopeptide antigen. Brooks CL, Schietinger A, Borisova SN, Kufer P, Okon M, Hirama T, Mackenzie CR, Wang LX, Schreiber H, Evans SV. Proc Natl Acad Sci U S A 107 10056-10061 (2010)
  2. Autoreactivity and exceptional CDR plasticity (but not unusual polyspecificity) hinder elicitation of the anti-HIV antibody 4E10. Finton KA, Larimore K, Larman HB, Friend D, Correnti C, Rupert PB, Elledge SJ, Greenberg PD, Strong RK. PLoS Pathog 9 e1003639 (2013)
  3. Large-scale analysis of somatic hypermutations in antibodies reveals which structural regions, positions and amino acids are modified to improve affinity. Burkovitz A, Sela-Culang I, Ofran Y. FEBS J 281 306-319 (2014)
  4. Efficient recovery of high-affinity antibodies from a single-chain Fab yeast display library. Walker LM, Bowley DR, Burton DR. J Mol Biol 389 365-375 (2009)
  5. Structure and dynamics of the anti-AMCV scFv(F8): effects of selected mutations on the antigen combining site. Arcangeli C, Cantale C, Galeffi P, Rosato V. J Struct Biol 164 119-133 (2008)
  6. Molecular description of flexibility in an antibody combining site. Zimmermann J, Romesberg FE, Brooks CL, Thorpe IF. J Phys Chem B 114 7359-7370 (2010)
  7. The structure of the anti-c-myc antibody 9E10 Fab fragment/epitope peptide complex reveals a novel binding mode dominated by the heavy chain hypervariable loops. Krauss N, Wessner H, Welfle K, Welfle H, Scholz C, Seifert M, Zubow K, Aÿ J, Hahn M, Scheerer P, Skerra A, Höhne W. Proteins 73 552-565 (2008)
  8. Editorial Microarray technology displays the complexities of the humoral immune response. Stafford P, Johnston S. Expert Rev Mol Diagn 11 5-8 (2011)
  9. Higher Affinity Antibodies Bind With Lower Hydration and Flexibility in Large Scale Simulations. Wong MTY, Kelm S, Liu X, Taylor RD, Baker T, Essex JW. Front Immunol 13 884110 (2022)
  10. Structural mechanism of Fab domain dissociation as a measure of interface stability. Pomarici ND, Waibl F, Quoika PK, Bujotzek A, Georges G, Fernández-Quintero ML, Liedl KR. J Comput Aided Mol Des 37 201-215 (2023)
  11. The Potential Role of Solvation in Antibody Recognition of the Lewis Y Antigen. Saha S, Murali R, Pashov A, Kieber-Emmons T. Monoclon Antib Immunodiagn Immunother 34 295-302 (2015)
  12. An in silico investigation on the binding site preference of PD-1 and PD-L1 for designing antibodies for targeted cancer therapy. Abdolmaleki S, Ganjalikhani Hakemi M, Ganjalikhany MR. PLoS One 19 e0304270 (2024)


Related citations provided by authors (1)

  1. Structural mechanism for affinity maturation of an anti-lysozyme antibody.. Cauerhff A, Goldbaum FA, Braden BC Proc Natl Acad Sci U S A 101 3539-44 (2004)

Quick links