The regulatory function of the human protein hnRNP A1 in splicing is believed to be mediated by multimerisation of individual hnRNP A1 units on long RNAs via an intrinsically disordered C-terminal domain [1]. The two N-terminal domains of hnRNP A1 are known to fold in a well-defined structure, which has been solved by X-ray crystallography, and more recently by solution NMR (pdb: 2LYV). The high degree of flexibility of the C-terminal domain, however, makes it inaccessible for both structural techniques. Using site-directed spin labelling, we determine distance distributions from residues in the structured domains, termed beacon sites, to individual residues in the disordered domain using the DEER pulsed EPR technique [2]. Together with a set of distances measured between the beacon sites themselves, it is then possible to calculate a spa-tial distribution of the position of a given residue in the disordered domain, which can be visualised as an isosurface of the probability density [3]. This analysis approach is included in the current version of the modelling software MMM [4].

Support: This work is supported by SNF grant 200020 157034.

[1] H. L. Okunola, A. R. Krainer, Cooperative-Binding and Splicing-Repressive Properties of hnRNP A1, Molecular and Cellular Biology, 2009, 29, 5620–5631
[2] G. Jeschke, DEER Distance Measurements on Proteins, Annual Review of Physical Chemistry, 2012, 63, 419–446
[3] G. Jeschke, Ensemble models of proteins and protein domains based on distance distribution restraints, Proteins, 2016, 84, 544–560
[4] G. Jeschke, Y. Polyhach, E. Bordignon, Multiscale Modeling of Macromolecules—MMM, 2010, ETH Zurich (http://www.epr.ethz.ch/software.html)