Different 3D domain-swapped oligomeric cyanovirin-N structures suggest trapped folding intermediates

作者：Koharudin Leonardus M I; Liu Lin; Gronenborn Angela M^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(19): 7702-7707.

DOI：10.1073/pnas.1300327110

• CV-N
• NMR spectroscopy
• protein folding
• X-ray structures

Although it has long been established that the amino acid sequence encodes the fold of a protein, how individual proteins arrive at their final conformation is still difficult to predict, especially for oligomeric structures. Here, we present a comprehensive characterization of oligomeric species of cyanovirin-N that all are formed by a polypeptide chain with the identical amino acid sequence. Structures of the oligomers were determined by X-ray crystallography, and each one exhibits 3D domain swapping. One unique 3D domain-swapped structure is observed for the trimer, while for both dimer and tetramer, two different 3D domain-swapped structures were obtained. In addition to the previously identified hinge-loop region of the 3D domain-swapped dimer, which resides between strands beta 5 and beta 6 in the middle of the polypeptide sequence, another hinge-loop region is observed between strands beta 7 and beta 8 in the structures. Plasticity in these two regions allows for variability in dihedral angles and concomitant differences in chain conformation that results in the differently 3D domain-swapped multimers. Based on all of the different structures, we propose possible folding pathways for this protein. Altogether, our results illuminate the amazing ability of cyanovirin-N to proceed down different folding paths and provide general insights into oligomer formation via 3D domain swapping.

• 出版日期2013-5-7