UCLA

Identifying polymer-forming SAM domains

Sterile Alpha Motif (SAM) domains are common protein modules in eukaryotic cells. It has not been possible to assign functions to uncharacterized SAM domains because they have been found to participate in diverse functions ranging from protein-protein interactions to RNA binding. Here we computationally identify likely members of the subclass of SAM domains that form polymers. Sequences were virtually threaded onto known polymer structures and then evaluated for compatibility with the polymer. We find that known SAM polymers score better than the vast majority of known non-polymers: 100% (7 of 7) of known polymers and only 8% of known non- polymers (1 of 12) score above a defined threshold value. Of 2901 SAM family members, we find 694 that score above the threshold and are likely polymers, including SAM domains from the proteins Lethal Malignant Brain Tumor, Bicaudal-C, Liprin-beta, Adenylate Cyclase and Atherin. In polymerization experiments, all of these predictions (except Adenylate Cyclase) were confirmed. As a result, the original SAM database was updated and additional predictions were obtained.

TMKink: A method to predict transmembrane helix kinks

A hallmark of membrane protein structure is the large number of distorted transmembrane helices. Because of the prevalence of bends, it is important to not only understand how they are generated but also to learn how to predict their occurrence. Here, we find that there are local sequence preferences in kinked helices, most notably a higher abundance of proline, which can be exploited to identify bends from sequence information. A neural network predictor identifies over two-thirds of all bends (sensitivity 0.70) with high reliability (specificity 0.89). It is likely that more structural data will allow for better helix distortion predictors with increased coverage in the future. The kink predictor, TMKink, is available at http://tmkinkpredictor.mbi.ucla.edu/.

Structural differences between mesophilic and thermophilic membrane proteins

Protein thermostability remains a focal point of interest for protein scientists. The differences in thermostability between mesophilic and thermophilic soluble proteins have been extensively studied. No differences in packing values have been found in soluble proteins. Membrane protein packing is different from soluble protein packing; thermophilic adaptation may be different as a result. Surprisingly, burial and packing values appear to be shared between mesophiles and thermophiles in both soluble and membrane proteins. We created a non-redundant database of unpaired and paired structures for the study of thermophile-mesophile structural differences in membrane proteins. We found little or no differences in burial or packing values in both the soluble and transmembrane regions of membrane proteins.