title: Tunnel plasticity and quaternary structural integrity of a pentameric protein ring.
abstract: Cyclic protein oligomers are common in cells. However, the importance of the residues that line the central tunnel of protein rings for overall architectural integrity is not well understood. To investigate the role of tunnel positions in protein assembly and stability, we prepared variants of the homo-pentameric lumazine synthase (LS) from Saccharomyces cerevisiae in which the three residues that line the middle of the tunnel were simultaneously changed. As a consequence of symmetry, these mutations cause a total of 15 changes in the structure of the pentameric complex. Detailed characterization of the variants indicates that they retain quaternary structural integrity, even in cases where the mutations induce considerable secondary structure alterations. The tunnels of symmetric ring-shaped proteins, such as LS, may consequently represent an overlooked site for protein engineering.
authors.affiliation: Laboratorium für Organische Chemie, ETH Zürich, CH-8093, Zürich, Switzerland.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Woycechowsky
authors.forename: Florian P
authors.initials: FP
authors.lastname: Seebeck
authors.forename: Donald
authors.initials: D
authors.lastname: Hilvert
mesh_terms: D000817:Anilino Naphthalenesulfonates / Q000378:metabolism*; D001665:Binding Sites; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry*; D012256:Riboflavin / Q000378:metabolism*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000817:Anilino Naphthalenesulfonates; D009097:Multienzyme Complexes; D011506:Proteins; C027132:1-anilino-8-naphthalenesulfonate; C044822:6,7-dimethyl-8-ribityllumazine synthase; D012256:Riboflavin