1IEH

SOLUTION STRUCTURE OF A SOLUBLE SINGLE-DOMAIN ANTIBODY WITH HYDROPHOBIC RESIDUES TYPICAL OF A VL/VH INTERFACE

Summary for 1IEH

• Entry DOI: 10.2210/pdb1ieh/pdb
• Descriptor: BRUC.D4.4 (1 entity in total)
• Functional Keywords: two pleated beta-sheet, immunoglobulin beta-barrel, immune system
• Biological source: Lama glama (llama)
• Total number of polymer chains: 1
• Total formula weight: 14618.01

Authors

Vranken, W.,Tolkatchev, D.,Xu, P.,Tanha, J.,Chen, Z.,Narang, S.,Ni, F. (deposition date: 2001-04-09, release date: 2002-08-07, Last modification date: 2024-10-30)

Primary citation

Vranken, W.,Tolkatchev, D.,Xu, P.,Tanha, J.,Chen, Z.,Narang, S.,Ni, F.
Solution structure of a llama single-domain antibody with hydrophobic residues typical of the VH/VL interface.
Biochemistry, 41:8570-8579, 2002

PubMed Abstract: 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 V(H)H 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 (15)N 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 F(v)s and camelid V(H)Hs with two pleated beta-sheets formed by four and five beta-strands. A canonical and undistorted beta-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 V(H)Hs; 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 V(H)H fragment HC-V, which may explain its enhanced solubility allowing NMR structural analysis.

PubMed: 12093273
DOI: 10.1021/bi012169a

Experimental method

SOLUTION NMR