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Vol. 16, Issue 7, 3128-3139, July 2005
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* Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454;
Departments of Biochemistry and Anatomy and Structural Biology, and Center for Synchrotron Biosciences, Albert Einstein College of Medicine, New York, NY 10461
Submitted January 24, 2005;
Revised April 11, 2005;
Accepted April 25, 2005
Monitoring Editor: Randy Schekman
Abp1 is a multidomain protein that regulates the Arp2/3 complex and links proteins involved in endocytosis to the actin cytoskeleton. All of the proposed cellular functions of Abp1 involve actin filament binding, yet the actin binding site(s) on Abp1 have not been identified, nor has the importance of actin binding for Abp1 localization and function in vivo been tested. Here, we report the crystal structure of the Saccharomyces cerevisiae Abp1 actin-binding actin depolymerizing factor homology (ADFH) domain and dissect its activities by mutagenesis. Abp1-ADFH domain and ADF/cofilin structures are similar, and they use conserved surfaces to bind actin; however, there are also key differences that help explain their differential effects on actin dynamics. Using point mutations, we demonstrate that actin binding is required for localization of Abp1 in vivo, the lethality caused by Abp1 overexpression, and the ability of Abp1 to activate Arp2/3 complex. Furthermore, we genetically uncouple ABP1 functions that overlap with SAC6, SLA1, and SLA2, showing they require distinct combinations of activities and interactions. Together, our data provide the first structural and functional view of the Abp1–actin interaction and show that Abp1 has distinct cellular roles as an adapter, linking different sets of ligands for each function.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Bruce L. Goode (goode{at}brandeis.edu).
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