Global analysis of VHHs framework regions with a structural alphabet

Autor: Floriane Noël, Alexandre G. de Brevern, Alain Malpertuy
Rok vydání: 2016
Předmět:
Models
Molecular
0301 basic medicine
Conformational change
Camelus
Protein domain
Immunoglobulin Variable Region
Structural diversity
Complementarity determining region
Computational biology
Crystallography
X-Ray
Quantitative Biology - Quantitative Methods
Biochemistry
Protein Structure
Secondary
03 medical and health sciences
Protein structure
Protein Domains
Species Specificity
Animals
Amino Acid Sequence
Protein secondary structure
Quantitative Methods (q-bio.QM)
Sequence Homology
Amino Acid
Chemistry
Structural variant
Biomolecules (q-bio.BM)
General Medicine
Complementarity Determining Regions
Crystallography
030104 developmental biology
Quantitative Biology - Biomolecules
FOS: Biological sciences
Structural alphabet
Binding Sites
Antibody
Immunoglobulin Heavy Chains
Camelids
New World
Zdroj: Biochimie. 131:11-19
ISSN: 0300-9084
Popis: The VHHs are antigen-binding region/domain of camelid heavy chain antibodies (HCAb). They have many interesting biotechnological and biomedical properties due to their small size, high solubility and stability, and high affinity and specificity for their antigens. HCAb and classical IgGs are evolutionary related and share a common fold. VHHs are composed of regions considered as constant, called the frameworks (FRs) connected by Complementarity Determining Regions (CDRs), a highly variable region that provide interaction with the epitope. Actually, no systematic structural analyses had been performed on VHH structures despite a significant number of structures. This work is the first study to analyse the structural diversity of FRs of VHHs. Using a structural alphabet that allows approximating the local conformation, we show that each of the four FRs do not have a unique structure but exhibit many structural variant patterns. Moreover, no direct simple link between the local conformational change and amino acid composition can be detected. These results indicate that long-range interactions affect the local conformation of FRs and impact the building of structural models.
Databáze: OpenAIRE
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