PUBLICATION: Response to The Challenges of Polydisperse SAXS Data Analysis – University of Copenhagen

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20 November 2015

PUBLICATION: Response to The Challenges of Polydisperse SAXS Data Analysis

Erlendsson, S., Arleth, L., Madsen K.L. Response to The Challenges of Polydisperse SAXS Data Analysis: Two Different SAXS Studies of PICK1 Produce Different Structural Models Structure  23(11), 1969–1970doi:10.1016/j.str.2015.10.008 (2015) I.F. 6.337

Abstract
PICK1 is a neuronal scaffolding protein containing a protein-binding PDZ domain and a membrane-binding BAR domain that mediate homo-dimerization (Xu and Xia, 2006-2007). The structure-function relationship of the protein has been worked with for more than a decade (Ammendrup-Johnsen et al., 2012Madsen et al., 2005Madsen et al., 2008 and Madsen et al., 2012), and we are very intrigued that this year has offered two solution structures of the protein (Karlsen et al., 2015 and Madasu et al., 2015). Both papers use SAXS data to obtain a model of the arrangement of the individual domains within PICK1, but the models differ considerably, in particular with respect to the positioning of the PDZ domains relative to the BAR domain. Madasu et al. (2015) suggest that the PDZ domains are associated with the BAR domain and the linker between the adjacent domain forms a helix, whereas we suggest that the PDZ domain is flexibly attached through an unstructured linker (Karlsen et al., 2015). This controversy is central to the understanding of PICK1 function, because the PDZ domain has been suggested to auto-inhibit the membrane-binding capacity of the BAR domain through steric hindrance (Citri et al., 2010Lu and Ziff, 2005 and Madsen et al., 2008). In a letter in this issue ofStructure, the Dominguez group now call into question our flexible PICK1 model and deem the two models mutually exclusive ( Boczkowska et al., 2015).

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