Gelsolin

The human mature gelsolin (GSN) is a 83 kDa protein composed of six homologous domains (named G1 to G6) connected by flexible linker regions, and is considered a master regulator of actin dynamics thanks to its severing and capping activities. GSN and the other members of the superfamily play an important role in several physiological processes, such as cell division and mobility, trafficking, signal transduction, immunomodulation and inflammation. In addition, GSN is responsible for a hereditary amyloidosis and it is involved in several other diseases, cancers in particular. Each GSN domain harbours a Ca2+ binding site and binding to the ion triggers local changes and domain rearrangements which shift the protein from a closed to an open conformation. In the absence of Ca2+, the actin binding sites are buried, limiting GSN ability to interact with actin filaments. In this inactive state, GSN can be crystallized but resolution is relatively low and several stretches of the protein too flexible to be modelled, such flexibility was shown to be relevant for GSN physiopathology. The experimental SAXS measurements were collected on a full-length GSN fused to a N-terminal His6-tag, corresponding to the sequence "MGSSHHHHHHSSGLVPRGSHMAS", resulting in a 778-residue protein.