4edn
From Proteopedia
Crystal structure of beta-parvin CH2 domain in complex with paxillin LD1 motif
Structural highlights
Function[PARVB_HUMAN] Adapter protein that plays a role in integrin signaling via ILK and in activation of the GTPases CDC42 and RAC1 by guanine exchange factors, such as ARHGEF6. Is involved in the reorganization of the actin cytoskeleton and formation of lamellipodia. Plays a role in cell adhesion, cell spreading, establishment or maintenance of cell polarity, and cell migration.[1] [2] [3] [4] [5] [PAXI_HUMAN] Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Publication Abstract from PubMedbeta-Parvin is a cytoplasmic adaptor protein that localizes to focal adhesions where it interacts with integrin-linked kinase and is involved in linking integrin receptors to the cytoskeleton. It has been reported that despite high sequence similarity to alpha-parvin, beta-parvin does not bind paxillin, suggesting distinct interactions and cellular functions for these two closely related parvins. Here, we reveal that beta-parvin binds directly and specifically to leucine-aspartic acid repeat (LD) motifs in paxillin via its C-terminal calponin homology (CH2) domain. We present the co-crystal structure of beta-parvin CH2 domain in complex with paxillin LD1 motif to 2.9 A resolution and find that the interaction is similar to that previously observed between alpha-parvin and paxillin LD1. We also present crystal structures of unbound beta-parvin CH2 domain at 2.1 A and 2.0 A resolution that show significant conformational flexibility in the N-terminal alpha-helix, suggesting an induced fit upon paxillin binding. We find that beta-parvin has specificity for the LD1, LD2, and LD4 motifs of paxillin, with K(D) values determined to 27, 42, and 73 mum, respectively, by surface plasmon resonance. Furthermore, we show that proper localization of beta-parvin to focal adhesions requires both the paxillin and integrin-linked kinase binding sites and that paxillin is important for early targeting of beta-parvin. These studies provide the first molecular details of beta-parvin binding to paxillin and help define the requirements for beta-parvin localization to focal adhesions. Structural Basis for Paxillin Binding and Focal Adhesion Targeting of beta-Parvin.,Stiegler AL, Draheim KM, Li X, Chayen NE, Calderwood DA, Boggon TJ J Biol Chem. 2012 Sep 21;287(39):32566-77. Epub 2012 Aug 6. PMID:22869380[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Boggon, T J | Calderwood, D A | Chayen, N E | Draheim, K M | Li, X | Stiegler, A L | Adaptor protein | Calponin homology domain | Focal adhesion | Integrin linked kinase | Integrin signaling | Ld motif | Paxillin | Protein-protein interaction | Signaling protein-cell adhesion complex
