Ca2+ Regulation of Gelsolin by Its C-terminal Tail

Gelsolin is activated by Ca 2+ to sever actin filaments. Ca 2+ regulation is conferred on the N-terminal half by the C-terminal half. This paper seeks to understand how Ca 2+ regulates gelsolin by testing the “tail helix latch hypothesis,” which is based on the structural data showing that gelso...

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Veröffentlicht in:The Journal of biological chemistry 2000-09, Vol.275 (36), p.27746-27752
Hauptverfasser: Lin, K M, Mejillano, M, Yin, H L
Format: Artikel
Sprache:eng
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Zusammenfassung:Gelsolin is activated by Ca 2+ to sever actin filaments. Ca 2+ regulation is conferred on the N-terminal half by the C-terminal half. This paper seeks to understand how Ca 2+ regulates gelsolin by testing the “tail helix latch hypothesis,” which is based on the structural data showing that gelsolin has a C-terminal tail helix that contacts the N-terminal half in the absence of Ca 2+ . Ca 2+ activation of gelsolin at 37 °C occurs in three steps, with apparent K d for Ca 2+ of 0.1, 0.3, and 6.4 × 10 −6 m . Tail helix truncation decreases the apparent Ca 2+ requirement for severing to 10 −7 m and eliminates the conformational change observed at 10 −6 m Ca 2+ . The large decrease in Ca 2+ requirement for severing is not due to a change in Ca 2+ binding nor to Ca 2+ -independent activation of the C-terminal half per se . Thus, the tail helix latch is primarily responsible for transmitting micromolar Ca 2+ information from the gelsolin C-terminal half to the N-terminal half. Occupation of submicromolar Ca 2+ -binding sites primes gelsolin for severing, but gelsolin cannot sever because the tail latch is still engaged. Unlatching the tail helix by 10 −6 m Ca 2+ releases the final constraint to initiate the severing cascade.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M003732200