3uaf | pdb_00003uaf
Crystal Structure of a TTR-52 mutant of C. elegans
Structural highlights
Function[TTR52_CAEEL] Plays a role as a bridging molecule that mediates recognition and engulfment of apoptotic cells by cross-linking the surface-exposed phosphatidylserine with the extracellular domain of the phagocyte receptor ced-1. Important for the generation of extracellular phosphatidylserine vesicles that promote loss of the exoplasmic leaflet from apoptotic cells in a time-dependent manner. Required for the exposure of exoplasmic leaflet on the phagocytic cells surrounding the apoptotic cells. Does not affect the phosphatidylserine externalization in living cells. May play a role in mediating transfer of phosphatidylserine from phosphatidylserine vesicles to ced-1 bearing phagocytes or alternatively result in the activation of a phosphatidylserine transporter in the phagocyte that promotes phosphatidylserine externalization.[1] [2] [3] Publication Abstract from PubMedDuring apoptosis, apoptotic cells are removed by professional phagocytes or neighboring engulfing cells either directly through phagocytic receptors or indirectly through bridging molecules that cross-link dying cells to phagocytes. However, how bridging molecules recognize "eat me" signals and phagocytic receptors to mediate engulfment remains unclear. Here, we report the structural and functional studies of Caenorhabditis elegans TTR-52, a recently identified bridging molecule that cross-links surface-exposed phosphatidylserine (PtdSer) on apoptotic cells to the CED-1 receptor on phagocytes. Crystal structure studies show that TTR-52 has an open beta-barrel-like structure with some similarities to the PKCalpha-C2 domain. TTR-52 is proposed to bind PtdSer via an "ion-mediating" PtdSer-binding mode. Intensive functional studies show that CED-1 binds TTR-52 through its N-terminal EMI domain and that the hydrophobic region of the TTR-52 C terminus is involved in this interaction. In addition, unlike other PtdSer-binding domains, TTR-52 forms dimers, and its dimerization is important for its function in vivo. Our results reveal the first full-length structure of a bridging molecule and the mechanism underlying bridging molecule-mediated apoptotic cell recognition. Structural study of TTR-52 reveals the mechanism by which a bridging molecule mediates apoptotic cell engulfment.,Kang Y, Zhao D, Liang H, Liu B, Zhang Y, Liu Q, Wang X, Liu Y Genes Dev. 2012 Jun 15;26(12):1339-50. PMID:22713871[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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