Abstract

Background: The chemokine receptors are an important subfamily of rhodopsin-like G protein-coupled receptors (GPCRs) and have fundamental roles in many physiological and pathological processes. Therefore, they are among the drug targets in pharmaceutical development.

Objective: The binding of these receptors with their chemokines is complex. The present work aims to contribute to a better understanding of this complexity.

Material and Methods: Several tools and statistical analysis were used on the composition of DNA and protein sequences of GPCRs including chemokine receptors.

Results: Our study reveals that these receptors have an uneven chromosomal distribution where the majority are located on chromosome 3 and are encoded by multiexonic genes. The principal component analysis, followed by hierarchical clustering, demonstrates that the composition in small amino acids, the extracellular region and the gene size have the highest ability to explain variability in the dataset. Besides this, XCR1, CCR1, CCR10 and CCR7 are the elements that best express the groups.

Finding Charge Clusters in Protein tool shows that negative clusters are localized only in the NTerminal segment then the positive clusters are localized in the C-Terminal domain, in the fifth and sixth transmembrane regions, more precisely at positions 208-209, 225-228.

ScanProsite analysis detects two intra-domain biological signatures frequently found with only few exceptions: glycosylation and sulfation domains localized especially in the N-Terminal tail, containing specific amino acids such as Ser, Thr, Asn and Tyr.

Conclusion: The identification of characteristics and classification of chemokine receptors are powerful approaches for discovering new features of their high-affinity interaction with chemokines.

Keywords: Charge cluster, classification, human chemokine receptors, prosite signatures, sequence analysis.

Graphical Abstract