Filamin A complexed with integrin beta 7 tail fragment
Homo sapiens (human)
Integrins are principal receptors in animal cells and function as transmembrane linkers, composed of a heterodimer of alpha and beta subunits. They transmit information from outside the cell to inside or reverse way, and also act as mechanical force of cells. In the extracellular region, they bind to extracellular matrix components including collagens, fibronectins and fibrinogens. On the other hand, in the intracellular region, those are connected with actin filaments, a cytoskeletal component to form cell shape, via anchor proteins, talin or filamin etc. For example, when we bleed, integrins play an important role. Before bleeding stops and scab created, emergent reactions occur in our body. Platelets activated either by contact with damaged blood vessels or by various soluble signal molecules stimulate beta subunit of integrin extracellular domain, and induce conformational change, causing binding to blood-clotting protein, fibrinogen. Fibrinogen links platelet to form a platelet plug, which stops bleeding.
The interaction between integrin extracellular domain and ligands is well studied, but little is known about an interaction between integrins and anchor proteins in molecular basis, with the exception of the beta-3 integrin-talin interaction.
The structure shown here shows an interface structure between integrin and one of anchor proteins, filamins. Filamins are homodimers of two 280kDa subunits, and each subunit contains an N-terminal actin binding domain. Filamins promote the formation of a loose and highly viscous gel by clamping together two actin filaments roughly at right angles. Filamins is though to be important to make assembly of complex networks linking transmenbrane receptors with signaling proteins and the actin cytoskeleton, but molecular basis mechanism or interface structure was not clear. Integlin binding domain (IgFLNa21) of filamin A was co-crystallized with a 31-residue peptide from the integrin beta 7 tail. The peptide formed an extended beta strand, and interacted with beta strands of the filamin immunoglobulin-like domain. This detailed structure information revealed that the binding site with filamin is overlapped with talin, indicating some special regulations may exist.
Protein Data Bank (PDB)
author: Sachiyo Nomura