Actin assembly is important for cell motility. The ability of actin subunits to join or leave filaments via the barbed end is critical to actin dynamics. Capping protein (CP) binds to barbed ends to prevent subunit gain and loss and is regulated by proteins that include V-1 and CARMIL. V-1 inhibits CP by sterically blocking one binding site for actin. CARMILs bind at a distal site and decrease the affinity of CP for actin, suggested to be caused by conformational changes. We used hydrogen-deuterium exchange with mass spectrometry (HDX-MS) to probe changes in structural dynamics induced by V-1 and CARMIL binding to CP. V-1 and CARMIL induce changes in both proteins’ binding sites on the surface of CP, along with a set of internal residues. Both also affect the conformation of CP's ββ subunit “tentacle,” a second distal actin-binding site. Concerted regulation of actin assembly by CP occurs through allosteric couplings between CP modulator and actin binding sites. Using hydrogen deuterium exchange mass spectrometry, Johnson et al. show how a key actin regulator, capping protein (CP), is allosterically controlled by two inhibitory proteins, CARMIL and V-1.

Original languageEnglish
Pages (from-to)2795-2804
Number of pages10
JournalCell Reports
Issue number9
StatePublished - May 29 2018


  • actin regulation
  • allostery
  • hydrogen-deuterium exchange
  • mass spectrometry


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