SOCS Box Domain

2020 ◽  
Author(s):  
Keyword(s):  
Socs Box

scholarly journals Insight into the HIV-1 Vif SOCS-box–ElonginBC interaction

Open Biology ◽  
2013 ◽  
Vol 3 (11) ◽  
pp. 130100 ◽  
Author(s):  
Zhisheng Lu ◽  
Julien R. C. Bergeron ◽  
R. Andrew Atkinson ◽  
Torsten Schaller ◽  
Dennis A. Veselkov ◽  
...  
Keyword(s):  
Solution Structure ◽  
Hydrophobic Interactions ◽  
Dynamic Information ◽  
Ubiquitin Ligase Complex ◽  
Biophysical Studies ◽  
Viral Infectivity Factor ◽  
Β Sheet ◽  
Socs Box ◽  
Insight Into ◽  
Hiv 1

The HIV-1 viral infectivity factor (Vif) neutralizes cell-encoded antiviral APOBEC3 proteins by recruiting a cellular ElonginB (EloB)/ElonginC (EloC)/Cullin5-containing ubiquitin ligase complex, resulting in APOBEC3 ubiquitination and proteolysis. The suppressors-of-cytokine-signalling-like domain (SOCS-box) of HIV-1 Vif is essential for E3 ligase engagement, and contains a BC box as well as an unusual proline-rich motif. Here, we report the NMR solution structure of the Vif SOCS–ElonginBC (EloBC) complex. In contrast to SOCS-boxes described in other proteins, the HIV-1 Vif SOCS-box contains only one α-helical domain followed by a β-sheet fold. The SOCS-box of Vif binds primarily to EloC by hydrophobic interactions. The functionally essential proline-rich motif mediates a direct but weak interaction with residues 101–104 of EloB, inducing a conformational change from an unstructured state to a structured state. The structure of the complex and biophysical studies provide detailed insight into the function of Vif's proline-rich motif and reveal novel dynamic information on the Vif–EloBC interaction.

scholarly journals The C-terminus of CIS defines its interaction pattern

2006 ◽  
Vol 401 (1) ◽  
pp. 257-267 ◽  
Author(s):  
Delphine Lavens ◽  
Peter Ulrichts ◽  
Dominiek Catteeuw ◽  
Kris Gevaert ◽  
Joël Vandekerckhove ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Receptor Activation ◽  
Sh2 Domain ◽  
Cytokine Receptor ◽  
Interaction Patterns ◽  
Death Domain ◽  
Intact Cells ◽  
C Terminus ◽  
Critical Binding ◽  
Socs Box

Proteins of the SOCS (suppressors of cytokine signalling) family are characterized by a conserved modular structure with pre-SH2 (Src homology 2), SH2 and SOCS-box domains. Several members, including CIS (cytokine-inducible SH2 protein), SOCS1 and SOCS3, are induced rapidly upon cytokine receptor activation and function in a negative-feedback loop, attenuating signalling at the receptor level. We used a recently developed mammalian two-hybrid system [MAPPIT (mammalian protein–protein interaction trap)] to analyse SOCS protein-interaction patterns in intact cells, allowing direct comparison with biological function. We find that, besides the SH2 domain, the C-terminal part of the CIS SOCS-box is required for functional interaction with the cytokine receptor motifs examined, but not with the N-terminal death domain of the TLR (Toll-like receptor) adaptor MyD88. Mutagenesis revealed that one single tyrosine residue at position 253 is a critical binding determinant. In contrast, substrate binding by the highly related SOCS2 protein, and also by SOCS1 and SOCS3, does not require their SOCS-box.

Targeting Lyn tyrosine kinase through protein fusions encompassing motifs of Cbp (Csk-binding protein) and the SOCS box of SOCS1

2012 ◽  
Vol 442 (3) ◽  
pp. 611-620 ◽  
Author(s):  
Rhiannon J. Whiting ◽  
Christine J. Payne ◽  
Jiulia Satiaputra ◽  
Nicole Kucera ◽  
Theresa W. Qiu ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Fluorescent Protein ◽  
Binding Protein ◽  
Proteasomal Degradation ◽  
Sh2 Domain ◽  
Protein Fusion ◽  
C Complex ◽  
Green Fluorescent ◽  
Socs Box

The tyrosine kinase Lyn is involved in oncogenic signalling in several leukaemias and solid tumours, and we have previously identified a pathway centred on Cbp [Csk (C-terminal Src kinase)-binding protein] that mediates both enzymatic inactivation, as well as proteasomal degradation of Lyn via phosphorylation-dependent recruitment of Csk (responsible for phosphorylating the inhibitory C-terminal tyrosine of Lyn) and SOCS1 (suppressor of cytokine signalling 1; an E3 ubiquitin ligase). In the present study we show that fusing specific functional motifs of Cbp and domains of SOCS1 together generates a novel molecule capable of directing the proteasomal degradation of Lyn. We have characterized the binding of pY (phospho-tyrosine) motifs of Cbp to SFK (Src-family kinase) SH2 (Src homology 2) domains, identifying those with high affinity and specificity for the SH2 domain of Lyn and that are preferred substrates of active Lyn. We then fused them to the SB (SOCS box) of SOCS1 to facilitate interaction with the ubiquitination-promoting elongin B/C complex. As an eGFP (enhanced green fluorescent protein) fusion, these proteins can direct the polyubiquitination and proteasomal degradation of active Lyn. Expressing this fusion protein in DU145 cancer cells (but not LNCaP or MCF-7 cells), that require Lyn signalling for survival, promotes loss of Lyn, loss of caspase 3, appearance of an apoptotic morphology and failure to survive/expand. These findings show how functional domains of Cbp and SOCS1 can be fused together to generate molecules capable of inhibiting the growth of cancer cells that express high levels of active Lyn.

scholarly journals Gonadotropin regulation of ankyrin-repeat and SOCS-box protein 9 (ASB9) in ovarian follicles and identification of binding partners

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0212571 ◽  
Author(s):  
Gabriel Benoit ◽  
Aly Warma ◽  
Jacques G. Lussier ◽  
Kalidou Ndiaye
Keyword(s):  
Ovarian Follicles ◽  
Ankyrin Repeat ◽  
Binding Partners ◽  
Socs Box
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