Abstract:To satisfy their iron needs, several gram‐negative bacteria use a heme uptake system that relies on the secretion in the extracellular medium of heme‐binding proteins called
HasA hemophores
. These proteins scavenge heme from the host, either free or hemoprotein‐bound, and shuttle it to a specific outer membrane transporter, HasR, whereby it is internalized by a TonB‐dependent process and then used as an iron source. HasA hemophores form a family of highly conserved 19–20 kDa proteins w… Show more
“…Once the linker is trapped by HasB, the formation of the inter-protein β-sheet stabilizes the position of the signalling domain, which would promote or stabilize its interaction with HasS. The latter is attached to the cytoplasmic membrane and recognizes the signalling domain via its periplasmic region, which is partially disordered and has an elongated shape [ 7 , 15 ]. These structural features of HasS and the location of the signalling domain towards the cytoplasmic membrane would favour the likelihood of their interaction and thus the signal transfer between the two membranes.…”
Section: Discussionmentioning
confidence: 99%
“…It belongs to the haem acquisition system (Has) developed by several Gram-negative bacteria to acquire haem as a source of iron [ 6 ]. In the present study, we focus on the Has system of Serratia marcescens , the first identified and intensely studied system [ 7 ]. HasR functions in synergy with HasA, a haem carrier protein.…”
In bacteria, some scarce nutrients are sensed, bound and internalized by their specific transporter. In the present study, using an integrative structural approach, we study HasR, a bacterial haem transporter in both its free and its loaded forms.
“…Once the linker is trapped by HasB, the formation of the inter-protein β-sheet stabilizes the position of the signalling domain, which would promote or stabilize its interaction with HasS. The latter is attached to the cytoplasmic membrane and recognizes the signalling domain via its periplasmic region, which is partially disordered and has an elongated shape [ 7 , 15 ]. These structural features of HasS and the location of the signalling domain towards the cytoplasmic membrane would favour the likelihood of their interaction and thus the signal transfer between the two membranes.…”
Section: Discussionmentioning
confidence: 99%
“…It belongs to the haem acquisition system (Has) developed by several Gram-negative bacteria to acquire haem as a source of iron [ 6 ]. In the present study, we focus on the Has system of Serratia marcescens , the first identified and intensely studied system [ 7 ]. HasR functions in synergy with HasA, a haem carrier protein.…”
In bacteria, some scarce nutrients are sensed, bound and internalized by their specific transporter. In the present study, using an integrative structural approach, we study HasR, a bacterial haem transporter in both its free and its loaded forms.
Bacteria use diverse signaling pathways to control gene expression in response to external stimuli. In Gram-negative bacteria, the binding of a nutrient is sensed by an outer membrane transporter. This signal is then transmitted to an antisigma factor and subsequently to the cytoplasm where an ECF sigma factor induces expression of genes related to the acquisition of this nutrient. The molecular interactions involved in this transmembrane signaling are poorly understood and structural data on this family of antisigma factor are rare. Here, we present the first structural study of the periplasmic domain of an antisigma factor and its interaction with the transporter. The study concerns the signaling in the heme acquisition system (Has) of Serratia marcescens. Our data support unprecedented partially disordered periplasmic domain of an anti-sigma factor HasS in contact with a membrane-mimicking environment. We solved the 3D structure of the signaling domain of HasR transporter and identified the residues at the HasS−HasR interface. Their conservation in several bacteria suggests wider significance of the proposed model for the understanding of bacterial transmembrane signaling.
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