期刊
PEERJ
卷 8, 期 -, 页码 -出版社
PEERJ INC
DOI: 10.7717/peerj.8408
关键词
Secondary structure; Nanobodies; Complementarity determining regions; Structural alphabet; Frameworks; Sequence structure relationship; Antibodies
资金
- Ministry of Research (France)
- University Paris Diderot, Sorbonne, Paris Cite (France)
- University of La Reunion, Reunion Island
- National Institute for Blood Transfusion (INTS, France)
- National Institute for Health and Medical Research (INSERM, France)
- labex GR-Ex
- program Investissements d'avenir'' of the French National Research Agency [ANR-11-LABX-0051, ANR-11-IDEX-0005-02]
- Indo-French Centre for the Promotion of Advanced Research/CEFIPRA [5302-2]
- Discngine, Paris, France
- ANRT, France
- Allocation de Recherche Reunion - Conseil Regional de la Reunion
- European Social Fund EU (ESF)
- GENCI (Grand Equipement National de Calcul Intensif) [A0010707621, A0040710426]
Antigen binding by antibodies requires precise orientation of the complementarity-determining region (CDR) loops in the variable domain to establish the correct contact surface. Members of the family Camelidae have a modified form of immunoglobulin gamma (IgG) with only heavy chains, called Heavy Chain only Antibodies (HCAb). Antigen binding in HCAbs is mediated by only three CDR loops from the single variable domain (VHH) at the N-terminus of each heavy chain. This feature of the VHH, along with their other important features, e.g., easy expression, small size, thermo-stability and hydrophilicity, made them promising candidates for therapeutics and diagnostics. Thus, to design better VHH domains, it is important to thoroughly understand their sequence and structure characteristics and relationship. In this study, sequence characteristics of VHH domains have been analysed in depth, along with their structural features using innovative approaches, namely a structural alphabet. An elaborate summary of various studies proposing structural models of VHH domains showed diversity in the algorithms used. Finally, a case study to elucidate the differences in structural models from single and multiple templates is presented. In this case study, along with the above-mentioned aspects of VHH, an exciting view of various factors in structure prediction of VHH, like template framework selection, is also discussed.
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