Title | Solution structures of a 30-residue amino-terminal domain of the carp granulin-1 protein and its amino-terminally truncated 3-30 subfragment: implications for the conformational stability of the stack of two beta-hairpins. |
Publication Type | Journal Article |
Year of Publication | 2002 |
Authors | Vranken, W. F., S. James, H. P. J. Bennett, and F. Ni |
Journal | Proteins |
Volume | 47 |
Issue | 1 |
Pagination | 14-24 |
Date Published | 2002 Apr 1 |
ISSN | 1097-0134 |
Keywords | Amino Acid Sequence, Animals, Carps, Intercellular Signaling Peptides and Proteins, Models, Chemical, Models, Molecular, Molecular Sequence Data, Nuclear Magnetic Resonance, Biomolecular, Numerical Analysis, Computer-Assisted, Peptide Fragments, Protein Structure, Secondary, Protein Structure, Tertiary, Proteins, Sequence Deletion |
Abstract | Carp granulins are members of an emerging class of proteins with a sequence motif encoding a parallel stack of two to four beta-hairpins. The carp granulin-1 protein forms a stack of four beta-hairpins, whereas its amino-terminal fragment appears to adopt a very stable stack of two beta-hairpins in solution. Here we determined a refined three-dimensional structure of this peptide fragment to examine potential conformational changes compared with the full-length protein. The structures were calculated with both a traditional method and a fast semiautomated method using ambiguous NMR distance restraints. The resulting sets of structures are very similar and show that a well-defined stack of two beta-hairpins is retained in the peptide. Conformational rearrangements compensating the loss of the carboxy-terminal subdomain of the native protein are restricted to the carboxy-terminal end of the peptide, the turn connecting the two beta-hairpins, and the Tyr(21) and Tyr(25) aromatic side chains. Further removal of the Val(1) and Ile(2) residues, which are part of the first beta-hairpin and components of two major hydrophobic clusters in the two beta-hairpin structure, results in the loss of the first beta-hairpin. The second beta-hairpin, which is closely associated with the first, retains a similar but somewhat less stable conformation. The invariable presence of the second beta-hairpin and the dependence of its stability on the first beta-hairpin suggest that the stack of two beta-hairpins may be an evolutionary conserved and autonomous folding unit. In addition, the high conformational stability makes the stack of two beta-hairpins an attractive scaffold for the development of peptide-based drug candidates. |
Alternate Journal | Proteins |
PubMed ID | 11870861 |
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