Biophysical Society Newsletter | October 2017

14

2017

BIOPHYSICAL SOCIETY NEWSLETTER

OCTOBER

Subgroups

IDP IDPs in Focus: Neurotransmitter Release The Intrinsically Disordered Protein (IDP) Subgroup focuses broadly on proteins that lack a stable 3D structure in their native state. The study of such proteins presents unique technical and conceptual challenges, which unite the subgroup. While once controversial, IDPs are now recog- nized as fundamentally important to biology. In particular, IDPs are frequently found in signal transduction pathways where their dynamic na- ture enables nuanced regulation of their activity. Neurotransmitter signaling involves the release of chemical neurotransmitters that are stored within synaptic vesicles. As such, their release requires the fusion of vesicles with the neuronal plasma membrane. Twenty years ago, Fasshauer and coworkers demonstrated that membrane fusion is catalyzed by a disorder-to-order transition in the SNARE (Soluble N-ethylmaleimide-sensitive fusion protein Attachment protein REceptor) proteins (Fasshauer 1997). Three SNARE pro- teins — two in the plasma membrane and one in the vesicle membrane — are largely disordered in isolation. However, these proteins bind together to form a four-helix bundle (Sutton 1998) with such extraordinary stability that disassembly requires an ATP-dependent chaperone in vivo (Sollner 1993). Experiments using NMR showed that SNARE protein assembly was directional, be- ginning at the N-terminus and proceeding to the C-terminal membrane anchors (Fiebig 1999). The folding of the complex brings the synaptic vesicle close to the plasma membrane wherein fusion is triggered. While the SNARE proteins begin in separate membranes, the SNARE complex ends up residing in the same membrane. Using optical tweezers, the energy liberated by the disorder- to-order transition has been estimated to be as high as 68 kBT (Ma 2015), which is one of the highest protein folding energies reported. Thus, neurotransmitter release is completely dependent on this family of IDPs.

References Fasshauer, D., H. Otto, W. K. Eliason, R. Jahn, and A. T. Brunger (1997). J Biol Chem 272(44): 28036–28041. Fiebig, K. M., L. M. Rice, E. Pollock, and A. T. Brunger (1999). Nat Struct Biol 6(2): 117–123. Ma, L., A. A. Rebane, G. Yang, Z. Xi, Y. Kang, Y. Gao, and Y. Zhang (2015). elife 4. Sollner, T., M. K. Bennett, S. W. Whiteheart, R. H. Scheller, and J. E. Rothman (1993). Cell 75(3): 409–418. Sutton, R. B., D. Fasshauer, R. Jahn, and A. T. Brunger (1998). Nature 395(6700): 347–353. The IDP Subgroup would like to bring the fol- lowing event to the attention of those with an interest in Intrinsically Disorder Proteins. Next spring (May 14–17, 2018), The European Molecular Biology Laboratory (EMBL) and the European Molecular Biology Organization (EMBO) will host a Symposium entitled Cellular Mechanisms Driven by Liquid Phase Separation. Liquid phase separation is emerging as a common biophysical basis underlying many important cel- lular functions and is frequently linked to IDPs. This conference will bring together scientists from soft matter polymer physics, molecular “un” structural biologists, cell biologists, and develop- mental biologists to shed light on the fascinating phenomena of phase separation in biology. To learn more, visit https://www.embo-embl-sympo- sia.org/symposia/2018/EES18-03/ Liquid Phase Penaration Symposium

Membrane Biophysics Call for Nominations

The Membrane Biophysics Subgroup is solicit- ing nominations for the 2018 Kenneth S. Cole Award. This is an annual award, given to an inves- tigator who has made a substantial contribution