The atomic coordinates and structure factors have been deposited in the Protein Data Bank under the accession numbers 5IR3 and 5C9K.

Background: 6a and 3r are the most implicated germ lines in light chain amyloidosis. Results: Mutagenesis at N-terminal, loop 40 -60, and CDR3 regions affected 3r fibrillogenesis. Conclusion: Changes at residues 7, 48, and 91 increased fibril formation while changes at residues 8 and 40 reverted fibrillogenesis. Significance: Characterization of light chain germ lines helps to identify key regions implicated in amyloidosis.

PAGE 2583:The method used to calculate the molar ellipticity of light chains at different temperatures from far UV CD spectra shown in Fig. 3 was incorrect. The calculations have now been performed correctly using the formula taken from Greenfield, N. J. (2006) Using circular dichroism spectra to estimate protein secondary structure. Nat. Protoc. 1, 2876 -2890 with [] ϭ millideg/(path length in millimeters ϫ the molar concentration of protein ϫ the number of residues). This correction does not affect the interpretation of the results or the conclusions of this work.

Mutating residues has been a common task in order to study structural properties of the protein of interest. Here, we propose and validate a simple method that allows the identification of structural determinants; i.e., residues essential for preservation of the stability of global structure, regardless of the protein topology. This method evaluates all of the residues in a 3D structure of a given globular protein by ranking them according to their connectivity and movement restrictions without topology constraints. Our results matched up with sequence-based predictors that look up for intrinsically disordered segments, suggesting that protein disorder can also be described with the proposed methodology.

Male sex hormones such as testosterone and dihydrotestosterone play important roles in several physiological and pathological processes. The biological activities of the aforementioned metabolites are mediated by the multidomain androgen receptor (AR), which is therefore a well-studied drug target. Ganoderma mushroom lanostanoid extracts have previously been shown to exert antiandrogenic activity; therefore, this work aims to identify which lanostane derivatives might act as selective ligands for AR. Because protein flexibility is of paramount importance for ligand binding, different conformations of AR were sampled to account for binding modes within a ligand binding site, then subjected to virtual screening against a metabolite library. Fifteen Ganoderma lanostanoids were selected as AR ligands, according to their calculated binding affinity to this nuclear receptor. The results show the relevance of certain structural and chemical aspects of our ligands, such as the presence of a ketonic group on C-3, which influences the process through which they bind to AR.