title: Structural diversity in a family of homologous proteins.
abstract: An interesting example of a structurally diverse group of sequentially homologous proteins is analyzed at the level of molecular interactions. In this family, the EF-hand calcium-binding proteins, there are examples of at least three distinct mutual positions of the N and C-terminal domains, despite significant sequence homology between all members of this family. Why does a particular protein choose one arrangement over another? To answer this question, detailed models of all proteins in their native structures as well as all alternative sequence/structure combinations are built by comparative modeling. By studying and comparing interactions stabilizing native structures and destabilizing alternative conformations, it is possible to gain insight into how such conformational diversity is achieved. It is shown that some mechanisms used to achieve it are: correlated mutations on the surface of two units and the presence of additional domains/chain fragments stabilizing desired topologies. The implications of these findings, both for structure predictions for other members of this family as well as the general problem of quaternary structure formation, are discussed.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Pawłowski
authors.forename: A
authors.initials: A
authors.lastname: Bierzyński
authors.forename: A
authors.initials: A
authors.lastname: Godzik
mesh_terms: D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D002147:Calmodulin / Q000737:chemistry; D005136:Eye Proteins; D051597:Hippocalcin; D008074:Lipoproteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009218:Myosins / Q000737:chemistry; D009419:Nerve Tissue Proteins; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization; D051603:Recoverin
chemical_list: D002135:Calcium-Binding Proteins; D002147:Calmodulin; D005136:Eye Proteins; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; D051603:Recoverin; D051597:Hippocalcin; D009218:Myosins