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

Download
  1. Get@NRC: Solution structure of a llama single-domain antibody with hydrophobic residues typical of the VH/VL interface (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1021/bi012169a
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleBiochemistry
Volume41
Issue27
Pages85708579; # of pages: 10
Subjectpha; human; structure
AbstractThe 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.
Publication date
LanguageEnglish
AffiliationNRC Biotechnology Research Institute; National Research Council Canada; NRC Institute for Biological Sciences
Peer reviewedNo
NRC number44840
VRAKEN2002
NPARC number3539104
Export citationExport as RIS
Report a correctionReport a correction
Record identifier02a0ac48-22d9-45fc-a9e6-4dd1b18258eb
Record created2009-03-01
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)