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• W2346613028 endingPage "160053" @default.
• W2346613028 startingPage "160053" @default.
• W2346613028 abstract "The vertebrate-specific proteins astrotactin-1 and 2 (ASTN-1 and ASTN-2) are integral membrane perforin-like proteins known to play critical roles in neurodevelopment, while ASTN-2 has been linked to the planar cell polarity pathway in hair cells. Genetic variations associated with them are linked to a variety of neurodevelopmental disorders and other neurological pathologies, including an advanced onset of Alzheimer's disease. Here we present the structure of the majority endosomal region of ASTN-2, showing it to consist of a unique combination of polypeptide folds: a perforin-like domain, a minimal epidermal growth factor-like module, a unique form of fibronectin type III domain and an annexin-like domain. The perforin-like domain differs from that of other members of the membrane attack complex-perforin (MACPF) protein family in ways that suggest ASTN-2 does not form pores. Structural and biophysical data show that ASTN-2 (but not ASTN-1) binds inositol triphosphates, suggesting a mechanism for membrane recognition or secondary messenger regulation of its activity. The annexin-like domain is closest in fold to repeat three of human annexin V and similarly binds calcium, and yet shares no sequence homology with it. Overall, our structure provides the first atomic-resolution description of a MACPF protein involved in development, while highlighting distinctive features of ASTN-2 responsible for its activity." @default.
• W2346613028 created "2016-06-24" @default.
• W2346613028 creator A5022147985 @default.
• W2346613028 creator A5036172001 @default.
• W2346613028 creator A5087686513 @default.
• W2346613028 date "2016-05-01" @default.
• W2346613028 modified "2023-10-16" @default.
• W2346613028 title "Structure of astrotactin-2: a conserved vertebrate-specific and perforin-like membrane protein involved in neuronal development" @default.
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