Identifying Unique Folds using RAPTOR for Protein Structure

Hui Li et al. recently investigated the transcriptional activity of C/EBP-A, and have published their findings in the Journal of Biological Chemistry, after identifying unique folds using RAPTOR for protein structure prediction. As the authors state, “transcription factor C/EBP is crucial for regulating transcription of genes involved in a number of diverse cellular processes, including those involved in some cytokine-induced responses. However, the mechanisms that contribute to its diverse transcriptional activity are not yet fully understood.” The use of transcriptional mediator regulates signal-induced cellular gene transcription from enhancer-bound transcription factors in the multi-subunit protein complex. As is the rising case with many researchers, the preferred method for determining the protein structure was completed successfully using RAPTOR.

The preference comes from its strength in hard targets, cases with low or no sequence homology. Typically, given a target protein sequence, comparison with a homologous protein with known structure can be found by using sequence search tools like PSI-BLAST or BLASTP. The target’s structure is then built from the known structure. However, when sequence homology is not significant, i.e. less than 25%, PSI-BLAST and BLASTP can not provide confident result. Unlike PSI-BLAST or BLASTP, which simply does a sequence search, protein threading (fold recognition) makes use of both homology and structure information. It scans the protein sequence with an unknown structure against a database of known structures. By using a scoring function and conducting compatibility analysis between three-dimensional structures and linear protein sequences, the best structural template will be identified from which to build the sequence’s structure. As a result, protein threading gives a superior prediction than homology modeling when there is no sequence homology. In this particular case domain confirmation was modeled in addition to accurately identifying the critical region of cellular factor of C/EBP. BSI would like to congratulate each researcher of this project on their investigation and findings. Contributing authors include: Hui Li, Padmaja Gade, Shreeram C. Nallar, Abhijit Raha, Sanjit K. Roy, Sreenivasu Karra, Janardan K. Reddy, Sekhar P. Reddy and Dhananjaya V. Kalvakolanu.