3FG6

Structure of the C-terminus of Adseverin

Summary for 3FG6

• Entry DOI: 10.2210/pdb3fg6/pdb
• Related: 1D0N 1P8X 1SVY 1h1v 2FH1
• Descriptor: Adseverin, CALCIUM ION (2 entities in total)
• Functional Keywords: c-terminus of adseverin, actin capping, actin-binding, cytoskeleton, phosphoprotein, actin-binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton : Q9Y6U3
• Total number of polymer chains: 8
• Total formula weight: 336329.11

Authors

Robinson, R.C. (deposition date: 2008-12-05, release date: 2009-08-11, Last modification date: 2023-11-01)

Primary citation

Chumnarnsilpa, S.,Lee, W.L.,Nag, S.,Kannan, B.,Larsson, M.,Burtnick, L.D.,Robinson, R.C.
The crystal structure of the C-terminus of adseverin reveals the actin-binding interface.
Proc.Natl.Acad.Sci.USA, 106:13719-13724, 2009

PubMed Abstract: Adseverin is a member of the calcium-regulated gelsolin superfamily of actin severing and capping proteins. Adseverin comprises 6 homologous domains (A1-A6), which share 60% identity with the 6 domains from gelsolin (G1-G6). Adseverin is truncated in comparison to gelsolin, lacking the C-terminal extension that masks the F-actin binding site in calcium-free gelsolin. Biochemical assays have indicated differences in the interaction of the C-terminal halves of adseverin and gelsolin with actin. Gelsolin contacts actin through a major site on G4 and a minor site on G6, whereas adseverin uses a site on A5. Here, we present the X-ray structure of the activated C-terminal half of adseverin (A4-A6). This structure is highly similar to that of the activated form of the C-terminal half of gelsolin (G4-G6), both in arrangement of domains and in the 3 bound calcium ions. Comparative analysis of the actin-binding surfaces observed in the G4-G6/actin structure suggests that adseverin in this conformation will also be able to interact with actin through A4 and A6, whereas the A5 surface is obscured. A single residue mutation in A4-A6 located at the predicted A4/actin interface completely abrogates actin sequestration. A model of calcium-free adseverin, constructed from the structure of gelsolin, predicts that in the absence of a gelsolin-like C-terminal extension the interaction between A2 and A6 provides the steric inhibition to prevent interaction with F-actin. We propose that calcium binding to the N terminus of adseverin dominates the activation process to expose the F-actin binding site on A2.

PubMed: 19666531
DOI: 10.1073/pnas.0812383106

Experimental method

X-RAY DIFFRACTION (3 Å)