Intrinsic structural disorder is a prevalent feature of proteins with chaperone activity. Using a complementary set of techniques, we have structurally characterized LjIDP1 (intrinsically disordered protein 1) from the model legume Lotus japonicus, and our results provide the first structural characterization of a member of the Lea5 protein family (PF03242). Contrary to in silico predictions, we show that LjIDP1 is intrinsically disordered and probably exists as an ensemble of conformations with limited residual -sheet, turn/loop, and polyproline II secondary structure. Furthermore, we show that LjIDP1 has an inherent propensity to undergo a large conformational shift, adopting a largely ␣-helical structure when it is dehydrated and in the presence of different detergents and alcohols. This is consistent with an overrepresentation of order-promoting residues in LjIDP1 compared with the average of intrinsically disordered proteins. In line with functioning as a chaperone, we show that LjIDP1 effectively prevents inactivation of two model enzymes under conditions that promote protein misfolding and aggregation. The LjIdp1 gene is expressed in all L. japonicus tissues tested. A higher expression level was found in the root tip proximal zone, in roots inoculated with compatible endosymbiotic M. loti, and in functional nitrogen-fixing root nodules. We suggest that the ability of LjIDP1 to prevent protein misfolding and aggregation may play a significant role in tissues, such as symbiotic root nodules, which are characterized by high metabolic activity.Intrinsically disordered (or natively unfolded) proteins (IDPs) 5 that are disordered along the entire amino acid chain or contain long disordered regions have recently attracted attention due to their role in important human diseases and their distinct functional features (1). In plants, a loosely defined group of stress-related proteins known as the late embryogenesis-abundant (LEA) proteins are characterized by being almost exclusively intrinsically disordered (reviewed by Tunnacliffe and Wise (2)). Several lines of evidence suggest a role of LEA proteins in the protection against damage caused by different types of stress, in particular desiccation, salt, and cold stress. The exact protection mechanism is unknown; however, the demonstrated ability of some (and probably most) LEA proteins to adopt a more well ordered conformation upon the addition of structure perturbing chemicals and when dried may contribute (2). Such structural plasticity is also known from other IDPs, which undergo disorder-to-order transitions upon ligand binding (3). However, specific ligand interactions have not been described for any LEA protein, and the mechanism by which LEA proteins assert their functions remains elusive.We report here the biochemical characterization of the LjIDP1 protein encoded by the LjIdp1 gene that is up-regulated during nodule development and in functional nitrogen-fixing nodules of the model legume Lotus japonicus. Leguminous plants are unique in their ability to ...