Discrete analysis of camelid variable domains: sequences, structures, and in-silico structure prediction

PeerJ

article

Akhila Melarkode Vattekatte¹  Nicolas Ken Shinada¹  Tarun J. Narwani¹  Floriane Noël¹  Olivier Bertrand¹  Jean-Philippe Meyniel⁸  Alain Malpertuy⁹  Jean-Christophe Gelly¹  Frédéric Cadet¹  Alexandre G. de Brevern¹ 

[1] Biologie Intégrée du Globule Rouge UMR_S1134;Laboratoire d’Excellence GR-Ex;Faculté des Sciences et Technologies;Institut National de la Transfusion Sanguine;Discngine SAS;PSL Research University, INSERM, UMR 932, Institut Curie;Université Paris Sud, Université Paris-Saclay;ISoft;Atragene;IBL;Peaccel, Protein Engineering Accelerator

关键词: Secondary structure;    Nanobodies;    Complementarity determining regions;    Structural alphabet;    Frameworks;    Sequence structure relationship;    Antibodies;   

DOI  :  10.7717/peerj.8408

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY