The structure of alpha-parvin CH2-paxillin LD1 complex reveals a novel modular recognition for focal adhesion assembly.
Alpha-parvin is an essential component of focal adhesions (FAs), which are large multiprotein complexes that link the plasma membrane and actin cytoskeleton. Alpha-parvin contains two calponin homology (CH) domains and its C-terminal CH2 domain binds multiple targets including paxillin LD motifs for regulating the FA network and signaling. Here we describe the solution structure of alpha-parvin CH2 bound to paxillin LD1. We show that although CH2 contains the canonical CH-fold, a previously defined N-terminal linker forms an alpha-helix that packs unexpectedly with the C-terminal helix of CH2, resulting in a novel variant of the CH domain. Importantly, such packing generates a hydrophobic surface that recognizes the Leu-rich face of paxillin-LD1, and the binding pattern differs drastically from the classical paxillin-LD binding to four-helix bundle proteins such as focal adhesion kinase. These results define a novel modular recognition mode and reveal how alpha-parvin associates with paxillin to mediate the FA assembly and signaling.
Structural Biology Program, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Xiaoxia
X
Wang
Koichi
K
Fukuda
In-Ja
IJ
Byeon
Algirdas
A
Velyvis
Chuanyue
C
Wu
Angela
A
Gronenborn
Jun
J
Qin
D000185:Actinin / Q000737:chemistry*; D000199:Actins / Q000737:chemistry*; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008840:Microfilament Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D051419:Paxillin / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000096985:Calponins
D000185:Actinin; D000199:Actins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008840:Microfilament Proteins; D051419:Paxillin; C486590:PARVA protein, human; D000096985:Calponins