The calcium‐dependent antibiotics (CDAs) are an important emerging class of antibiotics. The crystal structure of the CDA laspartomycin C in complex with calcium and the ligand geranyl‐phosphate at a resolution of 1.28 Å is reported. This is the first crystal structure of a CDA bound to its bacterial target. The structure is also the first to be reported for an antibiotic that binds the essential bacterial phospholipid undecaprenyl phosphate (C55‐P). These structural insights are of great value in the design of antibiotics capable of exploiting this unique bacterial target.

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Edited by Roger J. Colbran Murine paired immunoglobulin receptor B (PirB) and its human ortholog leukocyte immunoglobulin-like receptor B2 (LILRB2) are widely expressed inhibitory receptors that interact with a diverse set of extracellular ligands and exert functions ranging from down-regulation of immune responses to inhibition of neuronal growth. However, structural information that could shed light on how PirB interacts with its ligands is lacking. Here, we report crystal structures of the PirB ectodomain; the first full ectodomain structure for a LILR family member, at 3.3-4.5 Å resolution. The structures reveal that PirB's six Ig-like domains are arranged at acute angles, similar to the structures of leukocyte immunoglobulin-like receptor (LILR) and killer-cell immunoglobulin-like receptor (KIR). We observe that this regular arrangement is followed throughout the ectodomain, resulting in an extended zigzag conformation. In two out of the five structures reported here, the repeating zigzag is broken by the first domain that can adopt two alternative orientations. Quantitative binding experiments revealed a 9 M dissociation constant for PirB-myelin-associated glycoprotein (MAG) ectodomain interactions. Taken together, these structural findings and the observed PirB-MAG interactions are compatible with a model for intercellular signaling in which the PirB extracellular domains, which point away from the cell surface, enable interaction with ligands in trans. Mouse Paired immunoglobulin-like receptor B (PirB), 2 also named leukocyte immunoglobulin-like receptor subfamily B member 3 (LILRB3), is a promiscuous type I transmembrane receptor with diverse tissue-dependent functions, ranging from immune response modulation, hematopoietic stem cell consolidation to central nervous system plasticity regulation. To exert its cellular functions a diverse set of cell surface-expressed and secreted ligands interact with the PirB ectodomain. PirB is a member of the LILR family; LILRs are receptors for major histocompatibility complex class I (MHC-I) proteins and modulate the strength of immune responses by stimulatory (LILRAs) or inhibitory (LILRBs) signaling (1, 2). PirB is a functional ortholog of human LILRB2. As such, it is used as a mouse model to study LILRB2 function. PirB is expressed on various types of hematopoietic cells, where it down-regulates activation and differentiation. For example, through interaction with MHC-I molecules, PirB inhibits B-cell (3) and mast cell activation (4). Furthermore, through interaction with secreted angiopoietin-like proteins, PirB down-regulates blood platelet activation (5) and is involved in maintaining the stemness of hematopoietic stem cells (6). Unlike the other LILRB family members, PirB and LILRB2 are also expressed in neurons, where they are involved in restricting synaptic plasticity and neuronal regeneration. PirB and MHC-I regulate synaptic plasticity in the visual cortex (7, 8). In addition, PirB is found to be involved in Alzheimer's disease as a receptor for ␤-amyloid...

The calcium-dependent antibiotics (CDAs) are an important emerging class of antibiotics.The crystal structure of the CDAl aspartomycin Ci nc omplex with calcium and the ligand geranyl-phosphate at aresolution of 1.28 is reported. This is the first crystal structure of aCDA bound to its bacterial target. The structure is also the first to be reported for an antibiotic that binds the essential bacterial phospholipid undecaprenyl phosphate (C 55 -P). These structural insights are of great value in the design of antibiotics capable of exploiting this unique bacterial target.

The Nogo Receptor (NgR) is a glycophosphatidylinositol-anchored cell-surface protein and is a receptor for three myelin-associated inhibitors of regeneration: myelin-associated glycoprotein, Nogo66 and oligodendrocyte myelin glycoprotein. In combination with different co-receptors, NgR mediates signalling that reduces neuronal plasticity. The available structures of the NgR ligand-binding leucine-rich repeat (LRR) domain have an artificial disulfide pattern owing to truncated C-terminal construct boundaries. NgR has previously been shown to self-associateviaits LRR domain, but the structural basis of this interaction remains elusive. Here, crystal structures of the NgR LRR with a longer C-terminal segment and a native disulfide pattern are presented. An additional C-terminal loop proximal to the C-terminal LRR cap is stabilized by two newly formed disulfide bonds, but is otherwise mostly unstructured in the absence of any stabilizing interactions. NgR crystallized in six unique crystal forms, three of which share a crystal-packing interface. NgR crystal-packing interfaces from all eight unique crystal forms are compared in order to explore how NgR could self-interact on the neuronal plasma membrane.