title: A test of proposed rules for helix capping: implications for protein design.
abstract: alpha-helices within proteins are often terminated (capped) by distinctive configurations of the polypeptide chain. Two common arrangements are the Schellman motif and the alternative alpha(L) motif. Rose and coworkers developed stereochemical rules to identify the locations of such motifs in proteins of unknown structure based only on their amino acid sequences. To check the effectiveness of these rules, they made specific predictions regarding the structural and thermodynamic consequences of certain mutations in T4 lysozyme. We have constructed these mutants and show here that they have neither the structure nor the stability that was predicted. The results show the complexity of the protein-folding problem. Comparison of known protein structures may show that a characteristic sequence of amino acids (a sequence motif) corresponds to a conserved structural motif. In any particular protein, however, changes in other parts of the sequence may result in a different conformation. The structure is determined by sequence as a whole, not by parts considered in isolation.
authors.affiliation: Institute of Molecular Biology, Howard Hughes Medical Institute and Department of Physics, University of Oregon, Eugene, Oregon 97403-1229, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Sagermann
authors.forename: Lars-Göran
authors.initials: LG
authors.lastname: Mårtensson
authors.forename: Walter A
authors.initials: WA
authors.lastname: Baase
authors.forename: Brian W
authors.initials: BW
authors.lastname: Matthews
mesh_terms: D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry; D018360:Crystallography, X-Ray; D004795:Enzyme Stability; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry / Q000235:genetics; D016296:Mutagenesis; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D011506:Proteins; D009113:Muramidase