AI Article Synopsis
- Three types of proteins can initiate filament formation: the Arp2/3 complex, formins, and proteins with actin-binding WH2 domains, like Spire.
- Crystal structures of various Spire constructs reveal how they interact with actin, showing that the Spire CD domain is the smallest unit needed for actin nucleation.
- The structures formed by Spire have open configurations that differ from the tighter arrangements found in other nucleating proteins and in filamentous actin, indicating a unique way of starting filament growth.
Article Abstract
Three classes of proteins are known to nucleate new filaments: the Arp2/3 complex, formins, and the third group of proteins that contain ca. 25 amino acid long actin-binding Wiskott-Aldrich syndrome protein homology 2 domains, called the WH2 repeats. Crystal structures of the complexes between the actin-binding WH2 repeats of the Spire protein and actin were determined for the Spire single WH2 domain D, the double (SpirCD), triple (SpirBCD), quadruple (SpirABCD) domains, and an artificial Spire WH2 construct comprising three identical D repeats (SpirDDD). SpirCD represents the minimal functional core of Spire that can nucleate actin filaments. Packing in the crystals of the actin complexes with SpirCD, SpirBCD, SpirABCD, and SpirDDD shows the presence of two types of assemblies, "side-to-side" and "straight-longitudinal," which can serve as actin filament nuclei. The principal feature of these structures is their loose, open conformations, in which the sides of actins that normally constitute the inner interface core of a filament are flipped inside out. These Spire structures are distant from those seen in the filamentous nuclei of Arp2/3, formins, and in the F-actin filament.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900636 | PMC |
| http://dx.doi.org/10.1073/pnas.1005347107 | DOI Listing |
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