Contribution of CDR3 in characterization of camelid VHH and its aflatoxin B1-binding interaction

The single variable domain of heavy chain (VHH) antibodies, owing to their unique properties, has gained attention in immunoassays. However, compared with macromolecule antigens, in the case of small molecule haptens, such as aflatoxin B1 (AFB1), the role of the longer complementarity determining re...

Full description

Saved in:
Bibliographic Details
Main Authors: Hina Mukhtar, Lan Ma, Qian Pang, Xiaohong Wang, Jia Wang
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Food Chemistry Advances
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2772753X25000012
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850041614715584512
author Hina Mukhtar
Lan Ma
Qian Pang
Xiaohong Wang
Jia Wang
author_facet Hina Mukhtar
Lan Ma
Qian Pang
Xiaohong Wang
Jia Wang
author_sort Hina Mukhtar
collection DOAJ
description The single variable domain of heavy chain (VHH) antibodies, owing to their unique properties, has gained attention in immunoassays. However, compared with macromolecule antigens, in the case of small molecule haptens, such as aflatoxin B1 (AFB1), the role of the longer complementarity determining region 3 (CDR3) of VHH is still indistinct. In this study, anti-AFB1 VHH was selected from a naïve VHH library, and its CDR3 roles in VHH characteristics were further explored. Anti-AFB1 VHH-2 was selected with 6.33 × 10–5 M of KD value. Two VHH chimeras (C3-Nb28 and C3-VHH2) were constructed by interchanging the CDR3 of VHH-2 with Nb28, a previously reported anti-AFB1 VHH from immunized alpaca, and vice versa. Refolded C3-Nb28 was obtained from the inclusion body, and C3-VHH2 was purified as a soluble protein for prokaryotic expression. Computational analysis showed that the binding of VHH-2 to AFB1 is mediated by two hydrogen bonds (Thr106 and Tyr115) and two hydrophobic interactions (Trp109 and Thr114) in CDR3. In contrast, no binding pockets were available in the CDR3 in either VHH chimera, which was further confirmed by VHH ELISA. Studying the CDR3 role of VHH can elucidate its effects and affinity for small molecular weight molecules and broaden its applications.
format Article
id doaj-art-c2c03e183b4e40ab9ff6b2a0eef37056
institution DOAJ
issn 2772-753X
language English
publishDate 2025-03-01
publisher Elsevier
record_format Article
series Food Chemistry Advances
spelling doaj-art-c2c03e183b4e40ab9ff6b2a0eef370562025-08-20T02:55:44ZengElsevierFood Chemistry Advances2772-753X2025-03-01610088510.1016/j.focha.2025.100885Contribution of CDR3 in characterization of camelid VHH and its aflatoxin B1-binding interactionHina Mukhtar0Lan Ma1Qian Pang2Xiaohong Wang3Jia Wang4College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR ChinaCollege of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR ChinaCollege of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR ChinaCollege of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Key Laboratory of Environment Correlative Dietology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR ChinaCollege of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Key Laboratory of Environment Correlative Dietology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Corresponding author.The single variable domain of heavy chain (VHH) antibodies, owing to their unique properties, has gained attention in immunoassays. However, compared with macromolecule antigens, in the case of small molecule haptens, such as aflatoxin B1 (AFB1), the role of the longer complementarity determining region 3 (CDR3) of VHH is still indistinct. In this study, anti-AFB1 VHH was selected from a naïve VHH library, and its CDR3 roles in VHH characteristics were further explored. Anti-AFB1 VHH-2 was selected with 6.33 × 10–5 M of KD value. Two VHH chimeras (C3-Nb28 and C3-VHH2) were constructed by interchanging the CDR3 of VHH-2 with Nb28, a previously reported anti-AFB1 VHH from immunized alpaca, and vice versa. Refolded C3-Nb28 was obtained from the inclusion body, and C3-VHH2 was purified as a soluble protein for prokaryotic expression. Computational analysis showed that the binding of VHH-2 to AFB1 is mediated by two hydrogen bonds (Thr106 and Tyr115) and two hydrophobic interactions (Trp109 and Thr114) in CDR3. In contrast, no binding pockets were available in the CDR3 in either VHH chimera, which was further confirmed by VHH ELISA. Studying the CDR3 role of VHH can elucidate its effects and affinity for small molecular weight molecules and broaden its applications.http://www.sciencedirect.com/science/article/pii/S2772753X25000012VHHComplementarity determining regionAflatoxin B1VHH chimeraAntigen binding
spellingShingle Hina Mukhtar
Lan Ma
Qian Pang
Xiaohong Wang
Jia Wang
Contribution of CDR3 in characterization of camelid VHH and its aflatoxin B1-binding interaction
Food Chemistry Advances
VHH
Complementarity determining region
Aflatoxin B1
VHH chimera
Antigen binding
title Contribution of CDR3 in characterization of camelid VHH and its aflatoxin B1-binding interaction
title_full Contribution of CDR3 in characterization of camelid VHH and its aflatoxin B1-binding interaction
title_fullStr Contribution of CDR3 in characterization of camelid VHH and its aflatoxin B1-binding interaction
title_full_unstemmed Contribution of CDR3 in characterization of camelid VHH and its aflatoxin B1-binding interaction
title_short Contribution of CDR3 in characterization of camelid VHH and its aflatoxin B1-binding interaction
title_sort contribution of cdr3 in characterization of camelid vhh and its aflatoxin b1 binding interaction
topic VHH
Complementarity determining region
Aflatoxin B1
VHH chimera
Antigen binding
url http://www.sciencedirect.com/science/article/pii/S2772753X25000012
work_keys_str_mv AT hinamukhtar contributionofcdr3incharacterizationofcamelidvhhanditsaflatoxinb1bindinginteraction
AT lanma contributionofcdr3incharacterizationofcamelidvhhanditsaflatoxinb1bindinginteraction
AT qianpang contributionofcdr3incharacterizationofcamelidvhhanditsaflatoxinb1bindinginteraction
AT xiaohongwang contributionofcdr3incharacterizationofcamelidvhhanditsaflatoxinb1bindinginteraction
AT jiawang contributionofcdr3incharacterizationofcamelidvhhanditsaflatoxinb1bindinginteraction