Phospholamban complex structures

Structural studies of symmetric homo-oligomers (protein complexes with similar subunits arranged symmetrically) provide mechanistic insights into their roles in essential biological processes. We are developing algorithms for homo-oligomeric structure determination that are both complete, in that they evaluate all possible conformations, and data-driven, in that they evaluate conformations separately for consistency with experimental data and for quality of packing. Our algorithms determine homo-oligomeric structures by performing a branch-and-bound search in the symmetry configuration space, the space of symmetry axis parameters (positions and orientations) defining all possible Cn homo-oligomeric complexes for a fixed subunit structure. They eliminate those symmetry axes inconsistent with experimental inter-subunit distance restraints, and then identifies conformations representing any consistent, well-packed structure to within a user-defined similarity level. Our tests demonstrate the power of our methods to provide an unbiased determination and evaluation of homo-oligomeric complex structures.

The image above is from the complete ensemble of NMR structures of the unphosphorylated human phospholamban pentamer (pdb id 2hyn), as determined by our approach. We identified a set of 184 structures that represent to within 1 Angstrom all possible conformations that are consistent with the NMR data and have good van der Waals packing.