7m6t

Crystal structure of SOCS2/ElonginB/ElonginC bound to a non-canonical peptide that enhances phospho-peptide binding

spinqualitylabelsall models 7m6t, resolution 3.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7m6t is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.194Å Ligands: CAS, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SOCS2_HUMAN SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Publication Abstract from PubMed Suppressor of cytokine signaling (SOCS)2 protein is a key negative regulator of the growth hormone (GH) and Janus kinase (JAK)-Signal Transducers and Activators of Transcription (STAT) signaling cascade. The central SOCS2-Src homology 2 (SH2) domain is characteristic of the SOCS family proteins and is an important module that facilitates recognition of targets bearing phosphorylated tyrosine (pTyr) residues. Here we identify an exosite on the SOCS2-SH2 domain which, when bound to a non-phosphorylated peptide (F3), enhances SH2 affinity for canonical phosphorylated ligands. Solution of the SOCS2/F3 crystal structure reveals F3 as an alpha-helix which binds on the opposite side of the SH2 domain to the phosphopeptide binding site. F3:exosite binding appears to stabilise the SOCS2-SH2 domain, resulting in slower dissociation of phosphorylated ligands and consequently, enhances binding affinity. This biophysical enhancement of SH2:pTyr binding affinity translates to increase SOCS2 inhibition of GH signaling. Discovery of an exosite on the SOCS2-SH2 domain that enhances SH2 binding to phosphorylated ligands.,Linossi EM, Li K, Veggiani G, Tan C, Dehkhoda F, Hockings C, Calleja DJ, Keating N, Feltham R, Brooks AJ, Li SS, Sidhu SS, Babon JJ, Kershaw NJ, Nicholson SE Nat Commun. 2021 Dec 2;12(1):7032. doi: 10.1038/s41467-021-26983-5. PMID:34857742 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Elongation factor 3D structures

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