6uzj

NMR structure of the HACS1 SH3 domain

spinqualitylabelsall models 6uzj Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6uzj is a 1 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2kea. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SAMN1_HUMAN Negative regulator of B-cell activation. Down-regulates cell proliferation (in vitro). Promotes RAC1-dependent membrane ruffle formation and reorganization of the actin cytoskeleton. Regulates cell spreading and cell polarization. Stimulates HDAC1 activity. Regulates LYN activity by modulating its tyrosine phosphorylation (By similarity). Publication Abstract from PubMed Hematopoietic adaptor containing SH3 and SAM domains-1 (HACS1) is a signaling protein with two juxtaposed protein-protein interaction domains and an intrinsically unstructured region that spans half the sequence. Here, we describe the interaction between the HACS1 SH3 domain and a sequence near the third immunoreceptor tyrosine-based inhibition motif (ITIM3) of the paired immunoglobulin receptor B (PIRB). From surface plasmon resonance binding assays using a mouse and human PIRB ITIM3 phosphopeptides as ligands, the HACS1 SH3 domain and SHP2 N-terminal SH2 domain demonstrated comparable affinities in the micromolar range. Since the PIRB ITIM3 sequence represents an atypical ligand for an SH3 domain, we determined the NMR structure of the HACS1 SH3 domain and performed a chemical shift mapping study. This study showed that the binding site on the HACS1 SH3 domain for PIRB shares many of the same amino acids found in a canonical binding cleft normally associated with polyproline ligands. Molecular modeling suggests that the respective binding sites in PIRB ITIM3 for the HACS1 SH3 domain and the SHP2 SH2 domain are too close to permit simultaneous binding. As a result, the HACS1-PIRB partnership has the potential to amalgamate signaling pathways that influence both immune and neuronal cell fate. HACS1 signaling adaptor protein recognizes a motif in the paired immunoglobulin receptor B cytoplasmic domain.,Kwan JJ, Slavkovic S, Piazza M, Wang D, Dieckmann T, Johnson PE, Wen XY, Donaldson LW Commun Biol. 2020 Nov 13;3(1):672. doi: 10.1038/s42003-020-01397-z. PMID:33188360 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA