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 âtail helix latch hypothesis,â 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 |
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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 âtail helix latch hypothesis,â 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 37â°C occurs in three steps, with apparent K
d for Ca 2+ of 0.1, 0.3, and 6.4 Ã 10 â6 m . Tail helix truncation decreases the apparent Ca 2+ requirement for severing to 10 â7 m and eliminates the conformational change observed at 10 â6 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 â6 m Ca 2+ releases the final constraint to initiate the severing cascade. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M003732200 |