1I8X

SEMI-AUTOMATIC STRUCTURE DETERMINATION OF THE CG1 1-30 PEPTIDE BASED ON ARIA

Summary for 1I8X

• Entry DOI: 10.2210/pdb1i8x/pdb
• Related: 1qgm
• Descriptor: GRANULIN-1 (1 entity in total)
• Functional Keywords: two beta-hairpin stack, cytokine
• Total number of polymer chains: 1
• Total formula weight: 3195.60

Authors

Vranken, W.F.,James, S.,Bennett, H.P.J.,Ni, F. (deposition date: 2001-03-16, release date: 2002-04-17, Last modification date: 2021-10-27)

Primary citation

Vranken, W.F.,James, S.,Bennett, H.P.,Ni, F.
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.
Proteins, 47:14-24, 2002

PubMed 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.

PubMed: 11870861
DOI: 10.1002/prot.10077.abs

Experimental method

SOLUTION NMR