5c14
From Proteopedia
Crystal structure of PECAM-1 D1D2 domain
Structural highlights
FunctionPECA1_HUMAN Induces susceptibility to atherosclerosis (By similarity). Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions. Tyr-690 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes. Prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and changes function on apoptosis, promoting tethering of dying cells to phagocytes (the encounter of a viable cell with a phagocyte via the homophilic interaction of PECAM1 on both cell surfaces leads to the viable cell's active repulsion from the phagocyte. During apoptosis, the inside-out signaling of PECAM1 is somehow disabled so that the apoptotic cell does not actively reject the phagocyte anymore. The lack of this repulsion signal together with the interaction of the eat-me signals and their respective receptors causes the attachment of the apoptotic cell to the phagocyte, thus triggering the process of engulfment). Isoform Delta15 is unable to protect against apoptosis. Modulates BDKRB2 activation. Regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in human umbilical cord vein cells (HUVEC).[1] [2] [3] Publication Abstract from PubMedPECAM-1 is a 130 kDa member of the immunoglobulin gene (Ig) superfamily that is present on the surface of circulating platelets and leukocytes, and highly expressed at the junctions of confluent endothelial cell monolayers. PECAM-1-mediated homophilic interactions, known to be mediated by its two amino-terminal Ig homology domains, are essential for concentrating PECAM-1 at endothelial cell intercellular junctions, where it functions to facilitate diapedesis, maintain vascular integrity, and transmit survival signals into the cell. Given the importance of PECAM-1-mediated homophilic interactions in mediating each of these cell physiological events, and to reveal the nature and orientation of the PECAM-1-PECAM-1 homophilic binding interface, we undertook studies aimed at determining the crystal structure of the PECAM-1 homophilic binding domain, which is comprised of amino terminal Ig domains (IgD) 1 and 2. The crystal structure revealed that both IgD1 and IgD2 exhibit a classical IgSF fold, having a beta-sandwich topology formed by two sheets of antiparallel beta strands stabilized by the hallmark disulfide bond between the B and F strands. Interestingly, despite previous assignment to the C2 class of Ig-like domains, the structure of IgD1 reveals that it actually belongs to the I2-set of IgSF folds. Both Ig domains 1 and 2 participate importantly in the formation of the trans homophilic binding interface, with a total buried interface area of more than 2300 A2. These and other unique structural features of PECAM-1 allow for the development of an atomic-level model of the interactions that PECAM-1 forms during assembly of endothelial cell intercellular junctions. Structural basis for PECAM-1 homophilic binding.,Paddock C, Zhou D, Lertkiatmongkol P, Newman PJ, Zhu J Blood. 2015 Dec 23. pii: blood-2015-07-660092. PMID:26702061[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Newman P | Paddock C | Zhou D | Zhu J
