 Hi, I'm Jordan Chil, and I head the BioNMR laboratory at Barilang University, and this is my student guide. The structure and motions of proteins are what give them the ability to perform the biological function. What never ceases to fascinate me is how relatively simple principles of bioenergetics can produce such exquisitely controlled and efficient processes, without which life would not be possible. The association of two or more biomacromolecules lies at the very heart of the most basic cellular functions, such as enzyme catalysis, signaling, regulation, transport, and many important others. A very simple yet instructive example of how we can pinpoint the factors contributing to protein association is demonstrated by our recent publication in Protein Science, focusing on a tetramerization domain in the potassium channel KCSA. Hi, I'm Guy Kaminsky, and I'm wrapping up my PhD work in Jordan's lab, focusing on the biophysics of the cytoplasmic domain of KCSA. This channel is known to open a tasselic pH, but the gating role of its 40-C terminal residues, arranged as a four helix bundle, has been controversial. After establishing pH-dependent tetramerization in a previous paper, we set out to determine the molecular factors that control this tetramerization event. To do this, we systematically replaced residues along peptide from this region with alanine and measured the effect of each mutation on tetramerization. We discovered that the most important effect from an energetic standpoint was the interaction between hydrophobic residues lining the inner face of the helices. Surprisingly, a network of electrostatic intersubunic contacts that had been identified in an earlier crystal structure came in only second in influencing tetramer formation. Finally, even residues on the outer face of the helices are important, an effect we believe they exert by encouraging the helical conformation, which adds to tetramer stability. One particularly pleasing aspect of the study was the complementary nature of our different method. Sedimentation experiments provided dissociation constant for all tetrameres, NMR was sensitive to their own and off-rates of tetramerization process, and molecular dynamics played an important role in confirming these results. For the latter, we are grateful to Jing Fei Chen and Yishan Yaou from the Kindao Institute of Bioenergy and Biophoresis Technology in China. Thanks Guy. Don't be surprised by the important role of hydrophobics in holding the tetramer together. Hydrophobic forces are a dominating factor in the folding of most proteins. Remember that when identical proteins associate, there is never a contribution of a net charge effect. Apparently, the intricate layout of solpages and hydrogen bonds serves to fine-tune the tetrameric association, possibly by controlling the precise relative positioning of the four helical segments. We hope to extend this study in the future to full-length channels embedded in the carefully designed membrane mimicking environment. I'd like to thank our co-workers, Orel and Hadasa, for their contribution to this work. I'd like to thank you for your interest and wish you a happy reading.