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Open conformation of tetraspanins shapes interaction partner networks on cell membranes.

ABSTRACT: Tetraspanins, including CD53 and CD81, regulate a multitude of cellular processes through organizing an interaction network on cell membranes. Here, we report the crystal structure of CD53 in an open conformation poised for partner interaction. The large extracellular domain (EC2) of CD53 protrudes away from the membrane surface and exposes a variable region, which is identified by hydrogen-deuterium exchange as the common interface for CD53 and CD81 to bind partners. The EC2 orientation in CD53 is supported by an extracellular loop (EC1). At the closed conformation of CD81, however, EC2 disengages from EC1 and rotates toward the membrane, thereby preventing partner interaction. Structural simulation shows that EC1-EC2 interaction also supports the open conformation of CD81. Disrupting this interaction in CD81 impairs the accurate glycosylation of its CD19 partner, the target for leukemia immunotherapies. Moreover, EC1 mutations in CD53 prevent the chemotaxis of pre-B cells toward a chemokine that supports B-cell trafficking and homing within the bone marrow, a major CD53 function identified here. Overall, an open conformation is required for tetraspanin-partner interactions to support myriad cellular processes.

SUBMITTER: Yang Y

PROVIDER: S-EPMC7507038 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract:Potential protection from violence has been suggested as an explanation for women's preferences for more masculine partners. Previous studies, however, have not considered that violence may be multi-modal, and hence come from different sources. Therefore, we tested the effect of different fears of violence (i.e. vulnerability to public crime, likelihood of within-partnership violence) on masculinity preferences of women from Colombia, a country known for its high rates of violence. Eighty-three adult heterosexual women (mean age?±?SD?=?26.7?±?6.01) answered a survey that included questions about health (e.g. frequency of illnesses during the last year and during childhood), access to media (e.g. time spent watching television, frequency of internet use), education (i.e. highest level achieved) and violence perceptions. Participants' masculinity preferences for Salvadoran, European and Colombian male faces were recorded. Factor analysis revealed two different factors for the answers to questions related to violence. One factor loaded mostly on questions related to public violence and the second factor related to domestic violence. We found that women with higher scores on the domestic violence factor preferred significantly less masculine Colombian male faces. Even after controlling for participant age, education, access to media (TV and internet) and health-related factors, the domestic violence factor contributed significantly to explaining masculinity preferences. The results presented here suggest that women's preferences for masculinity may be a strategy to avoid aggressive partners and that the source of violence matters in mate choice. Significance statement:Women who perceive higher risks of domestic violence prefer less masculine looking partners. Using an experimental approach, we show that Colombian women who feel more in danger of violence within partnership prefer the faces of less masculine males. This was true even after controlling for women's education level, health and access to media.

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Open conformation of tetraspanins shapes interaction partner networks on cell membranes.

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