Unknown

Dataset Information

0

Molecular mechanisms underlying the evolution of the slp76 signalosome.


ABSTRACT: The well-defined mammalian slp76-signalosome is crucial for T-cell immune response, yet whether slp76-signalosome exists in invertebrates and how it evolved remain unknown. Here we investigated slp76-signalosome from an evolutionary perspective in amphioxus Branchiostoma belcheri (bb). We proved slp76-signalosome components bbslp76, bbGADS and bbItk are present in amphioxus and bbslp76 interacts with bbGADS and bbItk, but differences exist between the interaction manners within slp76-signalosome components of amphioxus and human (h). Specifically, bbslp76 has a unique WW-domain that blocked its association with hItk and decreased TCR-induced tyrosine-phosphorylation and NFAT-activation. Deletion of WW-domain shifted the constitutive association between bbslp76 and hPLC?1 to a TCR-enhanced association. Among slp76-signalosome, the interaction between slp76 and PLC?1 is the most conserved and the binding between Itk and slp76 evolved from constitutive to stimulation-regulated. Sequence alignment and 3D structural analysis of slp76-signalosome molecules from keystone species indicated slp76 evolved into a more unfolded and flexible adaptor due to lack of WW-domain and several low-complexity-regions (LCRs) while GADS turned into a larger protein by a LCR gain, thus preparing more space for nucleating the coevolving slp76-signalosome. Altogether, through deletion of WW-domain and manipulation of LCRs, slp76-signalosome evolves from a rigid and stimulation-insensitive to a more flexible and stimulation-responding complex.

SUBMITTER: Qu X 

PROVIDER: S-EPMC5431462 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Molecular mechanisms underlying the evolution of the slp76 signalosome.

Qu Xuemei X   Lan Xin X   Deng Chong C   Zhou Jiatao J   Du Jingjing J   Huang Shengfeng S   Li Yingqiu Y  

Scientific reports 20170504 1


The well-defined mammalian slp76-signalosome is crucial for T-cell immune response, yet whether slp76-signalosome exists in invertebrates and how it evolved remain unknown. Here we investigated slp76-signalosome from an evolutionary perspective in amphioxus Branchiostoma belcheri (bb). We proved slp76-signalosome components bbslp76, bbGADS and bbItk are present in amphioxus and bbslp76 interacts with bbGADS and bbItk, but differences exist between the interaction manners within slp76-signalosome  ...[more]

Similar Datasets

| S-EPMC5131788 | biostudies-literature
| S-EPMC4754300 | biostudies-literature
2011-10-05 | E-GEOD-32636 | biostudies-arrayexpress
| S-EPMC4977095 | biostudies-literature
| S-EPMC3536627 | biostudies-literature
| S-EPMC3935998 | biostudies-literature
2011-10-06 | GSE32636 | GEO
| S-EPMC1377642 | biostudies-other
| S-EPMC3530035 | biostudies-literature
| S-EPMC8383897 | biostudies-literature