Currently we have 509 structures out of the 511 glycans to the glycan array that has a coverage of 99. 6%. Virtual screening The ultimate stage during the practical classification of C style lec tins in our workflow is to screen for plausible interactions together with the glycan library by means of computational docking scientific studies. We use LigandFit, an algorithm that locates possi ble binding internet sites by analyzing cavities within the protein struc ture before endeavoring to dock every glycan from our virtual library. The output from this virtual screening is a record of glycans that have plausible poses in any in the predicted binding sites. Results and discussion Sequence Examination of CLEC17A We utilized our workflow on CLEC17A. a receptor that is expressed on dividing B cells in germinal centers. CLEC17A was 1st recognized and given the symbol through the HUGO Gene Nomenclature Committee.
However, substantially stays to selleck inhibitor be completed to eluci date its function and role during the immune method. Here we try to add for the know-how on CLEC17A by operating its amino acid sequence as a result of our examination workflow. The relevant sequence primarily based characteristics are summarized in Figure three. The full record of predicted functions is presented in Additional file two. Through the effects, CLEC17A can be a Kind II transmembrane protein. As being a C sort lectin, it really is predicted to possess a high specificity towards mannose and Ca2 due to the presence with the EPN motif and WND motif respectively. Inside of the extracellular area, you will find two predicted N linked glycosylated web sites. which could play a physiological position in the trans port and localization of CLEC17A to your cell surface. We utilised some of these outcomes to complement the experi psychological investigation and analysis of N linked glycosylation websites on CLEC17A To the cytoplasmic area, you will find numerous domains and motifs of interest.
Specifically, several SH2 and SH3 recognition domains is usually uncovered inside a proline selleckchem rich region. The same SH2 binding motifs are also pre dicted for being phosphorylated by proline directed kinases. A feasible candidate could be the mitogen activated protein kinase. This adds towards the self-assurance that SH2 containing proteins this kind of as the adaptor protein Grb2 and Src loved ones proteins can dock to your cytoplasmic tail of CLEC17A. A different doable intracellular signaling mechanism is usually inferred by the presence of hemi ITAM motifs. This motif, which can be also existing in Dectin one, can recruit and activate the Syk relatives kinases. Incidentally, Syk also has SH2 domains, supporting the hypothesis that it interacts with CLEC17A. Casein kinase II is predicted to become an additional kinase that could phosphorylate CLEC17A based mostly on its recognition motif. Following the consensus among Professional web page and ELM, the possible phosphorylation web pages had been shortlisted to positions sixteen, 42, and 68.