Comment on Three X-ray Crystal Structure Papers

Extract

Three recent papers published in The Journal of Immunology by Dr. Salunke and his coworkers at the National Institute of Immunology in New Delhi have attracted our attention (1–3). We regret to inform you that our findings cast serious doubt on the validity of the structural data presented in these publications. A paper published by the same group elsewhere exhibits similar problems (4).

To summarize, the publications in question attempt to address the role of plasticity in molecular recognition by Abs. Specifics vary from publication to publication, but the overall approach includes determination of multiple crystal structures of corresponding Abs in complex with various peptides. Based on the refined structure models, details of molecular recognition are then derived at an atomic level, and conclusions are presented regarding mechanisms of such recognition.

Unfortunately, in each of these publications describing peptide–Ab complexes determined by x-ray crystallography, the very central claim of a peptide actually bound to an Ab is not supported by evidence. The necessary evidence in the form of electron density is absent and the analyses of the experimental data are systematically flawed when examined according to accepted professional and scientific standards. Deposition of experimental data in the Protein Data Bank (PDB) has been mandatory since 2008, and availability of such data allows us (as well as anyone trained in protein crystallography) to verify the claims presented in the publications of Dr. Salunke. We inspected electron density maps for every protein–peptide complex structure associated with these papers, and found that the required primary experimental evidence, positive omit electron density in support of presented claims, is lacking. No electron density exists for the peptides in the purported protein–peptide complexes.