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Solution structure of a llama single-domain antibody with hydrophobic residues typical of the VH/VL interface

Par Conseil national de recherches du Canada

DOITrouver le DOI : https://doi.org/10.1021/bi012169a
AuteurRechercher : 1; Rechercher : 1; Rechercher : 1; Rechercher : 2; Rechercher : 1; Rechercher : 2; Rechercher : 1
Affiliation
  1. Conseil national de recherches du Canada. Institut de recherche en biotechnologie du CNRC
  2. Conseil national de recherches du Canada. Institut des sciences biologiques du CNRC
FormatTexte, Article
Sujetpharmaceutical; structure
Résumé
The three-dimensional structure of a llama single-domain antibody BrucD4-4 was established by use of solution NMR spectroscopy. BrucD4-4 has Val, Gly, Leu, and Trp residues at positions 37, 44, 45, and 47, which are considered to be a hallmark to distinguish llama VH from VHH fragments at the germline level. In contrast to the murine and human VHs, BrucD4-4 has sufficient solubility, is monomeric in solution, and displays high-quality NMR spectra characteristic of well-structured proteins. Amide proton/ deuterium exchange and the ¹⁵N relaxation data showed that BrucD4-4 has a classic protein structure with a well-packed core and comparatively mobile surface loops. The three-dimensional architecture of BrucD4-4 is analogous to that of VHs from murine and human Fvs and camelid VHHs with two pleated β-sheets formed by four and five β-strands. A canonical and undistorted β-barrel exposes a number of hydrophobic residues into the solvent on the surface of the three-dimensional structure. The eight-residue H3 loop folds over the side chain of Val37 similarly to that in llama VHHs; however, this interaction may be transient due to the H3 conformational flexibility. Overall, the surface characteristics of BrucD4-4 with respect to hydrophobicity appear to lie between the human VH domain from Fv Pot and the llama VHH fragment HC-V, which may explain its enhanced solubility allowing NMR structural analysis.
Date de publication
Dans
  • Biochemistry 41, nº 27 (11 juin 2002) : 8570–8579.
Langueanglais
Numéro du CNRC44840
VRAKEN2002
Numéro NPARC3539104
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Identificateur de l’enregistrement02a0ac48-22d9-45fc-a9e6-4dd1b18258eb
Enregistrement créé2009-03-01
Enregistrement modifié2020-03-30
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