2woz
From Proteopedia
The novel beta-propeller of the BTB-Kelch protein Krp1 provides the binding site for Lasp-1 that is necessary for pseudopodia extension
Structural highlights
FunctionKLH41_RAT Involved in skeletal muscle development and differentiation. Regulates proliferation and differentiation of myoblasts and plays a role in myofibril assembly by promoting lateral fusion of adjacent thin fibrils into mature, wide myofibrils. Required for pseudopod elongation in transformed cells.[UniProtKB:A2AUC9][1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedKelch-related protein 1 (Krp1) is up-regulated in oncogene-transformed fibroblasts. The Kelch repeats interact directly with the actin-binding protein Lasp-1 in membrane ruffles at the tips of pseudopodia, where both proteins are necessary for pseudopodial elongation. Herein, we investigate the molecular basis for this interaction. Probing an array of overlapping decapeptides of Rattus norvegicus (Rat) Krp1 with recombinant Lasp-1 revealed two binding sites; one ((317)YDPMENECYLT(327)) precedes the first of five Kelch repeats, and the other ((563)TEVNDIWKYEDD(574)) is in the last of the five Kelch repeats. Mutational analysis established that both binding sites are necessary for Krp1-Lasp-1 interaction in vitro and function in vivo. The crystal structure of the C-terminal domain of rat Krp1 (amino acids 289-606) reveals that both binding sites are brought into close proximity by the formation of a novel six-bladed beta-propeller, where the first blade is not formed by a Kelch repeat. Novel beta-propeller of the BTB-Kelch protein Krp1 provides a binding site for Lasp-1 that is necessary for pseudopodial extension.,Gray CH, McGarry LC, Spence HJ, Riboldi-Tunnicliffe A, Ozanne BW J Biol Chem. 2009 Oct 30;284(44):30498-507. Epub 2009 Sep 2. PMID:19726686[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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