Citrullination of adenosine deaminase impairs its binding to dipeptidyl peptidase IV
The presence of citrullinated adenosine deaminase (ADA) was reported in the synovial fluids of rheumatoid arthritis individuals. This work reports the effects of ADA citrullination on the formation/stabilization of ADA complex with dipeptidyl peptidase IV (DPPIV). The electrophoretic mobility of in...
Saved in:
Published in | Biophysical chemistry Vol. 286; p. 106820 |
---|---|
Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier B.V
01.07.2022
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The presence of citrullinated adenosine deaminase (ADA) was reported in the synovial fluids of rheumatoid arthritis individuals. This work reports the effects of ADA citrullination on the formation/stabilization of ADA complex with dipeptidyl peptidase IV (DPPIV). The electrophoretic mobility of in vivo citrullinated ADA was diminished compared to the native one. The biosensor binding study demonstrated approximately four-fold lower affinity of both in vivo and in vitro citrullinated ADAs to DPPIV (KD = 161 ± 51.3 and 171 ± 52.2 nM, respectively) compared with wild ADA (KD = 38 ± 9.4 nM). These results were confirmed by examining the ADA interaction with DPPIV using size-exclusion chromatography and fluorescence anisotropy methods. The computational modeling of Arg142 → Cit142 modification in ADA showed a local structural rearrangement and a less favorable binding affinity to DPPIV. According to these observations, citrullinated ADA being a possible target triggering autoimmunity hinders also the formation of ADA-DPPIV complex, essential in immune system function.
[Display omitted]
•Citrullinated in vivo adenosine deaminase (ADA) is reduced electrophoretic mobility.•Arg142 → Cit142 modification rearranges ADA structure, decreases its affinity to DPPIV.•Biosensor, fluorescence anysotropy, size-exclusion chromatography methods are used.•Citrullinated ADA affinity to DPPIV is four-fold lower than of wild ADA.•Citrullinated ADA, being immune system target, hinders formation of ADA-DPPIV complex. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0301-4622 1873-4200 |
DOI: | 10.1016/j.bpc.2022.106820 |