| Autor: |
Zhang, Y., Vorobiev, Sergey M., Gibson, Bruce G., Binghua Hao, Sidhu, Gurjit S., Mishra, Vishnu S., Yarmola, Elena G., Bubb, Michael R., Almo, Steven C., Southwick, Frederick S. |
| Předmět: |
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| Zdroj: |
EMBO Journal; 9/27/2006, Vol. 25 Issue 19, p4458-4467, 10p |
| Abstrakt: |
CapG is the only member of the gelsolin family unable to sever actin filaments. Changing amino acids 84-91 (severing domain) and 124-137 (WH2-containing segment) simultaneously to the sequences of gelsolin results in a mutant, CapG-sev, capable of severing actin filaments. The gain of severing function does not alter actin filament capping, but is accompanied by a higher affinity for monomeric actin, and the capacity to bind and sequester two actin monomers. Analysis of CapG-sev crystal structure suggests a more loosely folded inactive conformation than gelsolin, with a shorter S1-S2 latch. Calcium binding to S1 opens this latch and S1 becomes separated from a closely interfaced S2-S3 complex by an extended arm consisting of amino acids 118-137. Modeling with F-actin predicts that the length of this WH2-containing arm is critical for severing function, and the addition of a single amino acid (alanine or histidine) eliminates CapG-sev severing activity, confirming this prediction. We conclude that efficient severing utilizes two actin monomer-binding sites, and that the length of the WH2-containing segment is a critical functional determinant for severing. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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