INVESTIGADORES
DELFINO Jose Maria
artículos
Título:
Dissection of a beta-barrel motif leads to a functional dimer: The case of the intestinal fatty acid binding protein
Autor/es:
GR FRANCHINI; LM CURTO; JJ CARAMELO; JM DELFINO
Revista:
PROTEIN SCIENCE
Editorial:
JOHN WILEY & SONS INC
Referencias:
Año: 2009 vol. 18 p. 2592 - 2602
ISSN:
0961-8368
Resumen:
A lingering issue in the area of protein engineering is the optimal design of b motifs. In
this regard, the framework provided by intestinal fatty acid binding protein (IFABP) was
successfully chosen to explore the consequences on structure and function of the redesign of
natural motifs. A truncated form of IFABP (D98D) served to illustrate the nonintuitive notion that the
integrity of the b-barrel can indeed be compromised with no effect on the ability to attain a nativelike fold. This is most likely the outcome of the key role played by the preservation of essential
core residues. In the search for the minimal structural determinants of this fold, D98D offered room
for further intervention. A dissection of this protein leads to a new abridged variant, D78D,
containing 60% of the amino acids of IFABP. Spectroscopic analyses indicate that D78D retains
substantial b-sheet content and preserves tertiary interactions, displaying cooperative unfolding
and binding activity. Most strikingly, this construct adopts a remarkably stable dimeric structure in
solution. This phenomenon takes advantage of the inherent structural plasticity of this motif, likely
profitting from edge-to-edge interactions between b-sheets, whereas avoiding the most commonly
occurring outcome represented by aggregation.