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A conserved sequence in the small intracellular loop of tetraspanins forms an M-shaped inter-helix turn.

ABSTRACT: Tetraspanins are a family of small proteins with four transmembrane segments (TMSs) playing multiple roles in human physiology. Nevertheless, we know little about the factors determining their structure. In the study at hand, we focus on the small intracellular loop (SIL) between TMS2 and TMS3. There we have identified a conserved five amino acid core region with three charged residues forming an M-shaped backbone, which we call M-motif. The M´s plane runs parallel to the membrane surface and the central amino acid constitutes the inter-helix turning point. At the second position of the M-motif, in tetraspanin crystal structures we identified a glutamate oriented towards a lysine in the juxtamembrane region of TMS1. Using Tspan17 as example, we find that by mutating either the glutamate or juxtamembrane-lysine, but not upon glutamate/lysine swapping, expression level, maturation and ER-exit are reduced. We conclude that the SIL is more than a short linking segment but propose it is involved in shaping the tertiary structure of tetraspanins.

SUBMITTER: Reppert N

PROVIDER: S-EPMC8927573 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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A conserved sequence in the small intracellular loop of tetraspanins forms an M-shaped inter-helix turn.

Reppert Nikolas N Lang Thorsten T

Scientific reports 20220316 1

Tetraspanins are a family of small proteins with four transmembrane segments (TMSs) playing multiple roles in human physiology. Nevertheless, we know little about the factors determining their structure. In the study at hand, we focus on the small intracellular loop (SIL) between TMS2 and TMS3. There we have identified a conserved five amino acid core region with three charged residues forming an M-shaped backbone, which we call M-motif. The M´s plane runs parallel to the membrane surface and th ...[more]

PMID: 35296690

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Project description:Inter-cellular and inter-kingdom signaling systems of various levels of complexity regulate pathogenic and mutualistic interactions between bacteria, parasites, and fungi and animal and plant hosts. Inter-kingdom interactions between mutualistic bacteria such as rhizobia and legumes during nodulation and between fungi and plants during mycorrhizal associations, are characterized by the extensive exchange of molecular signals, which allow nitrogen and phosphate assimilation, respectively. A novel aspect of this signaling exchange is the existence of specific structures, the exosomes, that carry important molecules that shape the plant-pathogen interactions. Exosomes contain a wide array of molecules, such as lipids, proteins, messenger RNA, and microRNAs, that play important roles in cell-to-cell communication in animal and plant cells by affecting gene expression and other physiological activity in distant cells within the same organism (e.g., during cancer metastases and neuron injuries). In plant cells, it has been recently reported that exosomes go beyond organism boundaries and inhibit a pathogenic interaction in plants. Plant produce and send exosomes loaded with specific small miRNA which inhibit the pathogen infection, but the pathogen can also produce exosomes carrying pro-pathogenic proteins and microRNAs. Therefore, exosomes are the important bridge regulating the signal exchange. Exosomes are small membrane-bound vesicles derived from multivesicular bodies (MVBs), which carries selected cargos from the cytoplasm (protein, lipids, and microRNAs) and under certain circumstances, they fuse with the plasma membrane, releasing the small vesicles as cargo-carrying exosomes into the extracellular space during intercellular and inter-kingdom communication. Animal and plant proteomic studies have demonstrated that tetraspanin proteins are an integral part of exosome membranes, positioning tetraspanins as essential components for endosome organization, with key roles in membrane fusion, cell trafficking, and membrane recognition. We discuss the similarities and differences between animal tetraspanins and plant tetraspanins formed during plant-microbe interactions and their potential role in mutualistic communication.

Dataset Information

A conserved sequence in the small intracellular loop of tetraspanins forms an M-shaped inter-helix turn.

Publications

A conserved sequence in the small intracellular loop of tetraspanins forms an M-shaped inter-helix turn.

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