One thing I look forward to at the Biophysical Society meeting is the New and Notable session. This year was no different and I found two of the talks particular interesting given my background (structural biology). This does not mean the others were not fantastic – they were. Rather, it’s that like everyone else I have my own biases towards the things I pay attention to. That said, let me share some of my excitement with you
Carol Robinson (Oxford Univ.) started off with a fantastic set of results showing intact membrane complexes put into the mass spectrometer! Anyone who pays attention to the study of the structures of membrane complexes is well aware of how difficult investigating these structures can be. Similarly, it is not really all that common (until Carol came into the picture) to be putting large complexes into a mass spectrometer and obtaining useful results that gave us additional insights into biology.
What Carol showed was V-type ATPases: complexes that have not been crystallized which she and her group then proceeded to stick in the mass spec. The talk wowed me with one particular slide. It was a slide showing the intact ATPase from Thermus thermophilus in the mass spec.
What the results she showed did was demonstrate that the use of the mass spec techniques innovated in her laboratory could do was give insights into the mechanism of switching from pumping to synthesis of the ATPases. I found it a particularly intriguing talk and a very effective communication of the results.
Seok-Yong Lee (Duke Univ.) showed the x-ray structure of a Concentrative Nucleoside Transporter (CNT) from Vibrio Cholerae. As a background he described that the CNT is a membrane bound transporter to get nucleoside into the cell through an ion gradient. He then gave a good description of just why this was interesting, in that the system has real potential for providing a platform for drug design and delivery.
Next, Seok-Yong dove into showing and describing the 2.4A structure solved in his laboratory that was done in complex with uridine: it is a beautiful trimer structure.
Next, he showed that he was able to determine the stoichiometry after determining the structure. It was a great explanation of how the structure determination aided in the next determining the next biochemical experiment that they would perform and guiding with insights what to look for.
Similarly, the structure allowed him to identify and annotate the transport domain of the protein, and the nucleoside binding site. Because CNT uses a sodium gradient, that binding site is important. The sodium is coordinated by both backbone COO and sidechain positions nearby. This sodium binding site must be coupled with the ucleoside binding, and as he showed, the two are very close to one another. The critical residues for the base of the nucleoside are brought together by stabilizing interactions from the sodium being bound into the CNT. As sodium dissociates, this triggers the dissociation of the nucleoside in the binding site.
All told, it was a fascinating talk and the determination of the structure using crystallography allowed for a nice tale of biochemical experiments that followed from insights gained by solving the structure. It is no wonder this was selected for the New and Notable!