Romano, Sebastian A.
Lima, Luis Mauricio T. R.
Lopes, Marilene H.
Silva, Jerson L.
Número total de Autores: 7
Afiliação do(s) autor(es):
 Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio De Janeiro - Brazil
 Univ Fed Rio de Janeiro, Fac Farm, BR-21941 Rio De Janeiro - Brazil
 Ludwig Inst Canc Res, Sao Paulo - Brazil
 Univ Fed Rio de Janeiro, Inst Bioquim Med, BR-21941 Rio De Janeiro - Brazil
Número total de Afiliações: 4
Tipo de documento:
Citações Web of Science:
The glycosylphosphatidylinositol (GPI)anchored prion protein (PrPC), usually associated with neurodegenerative diseases, modulates various cellular responses and may scaffold multiprotein cell surface signaling complexes. Engagement of PrPC with the secret-able cochaperone hop/STI1 induces neurotrophic transmembrane signals through unknown molecular mechanisms. We addressed whether interaction of PrPC and hop/STI1 entails structural rearrangements relevant for signaling. Using recombinant wild-type and mutant mouse proteins and binding peptides, we measured circular dichroism (CD), fluorescence spectroscopy, and small angle X-ray scattering (SAXS). PrPC: hop/STI1 interaction triggers loss of PrP helical structures, involving at least a perturbation of the PrP(143-153) alpha-helix, but no secondary structural modification of hop/STI1 was detected. Novel SAXS models revealed a significant C-terminal compaction of hop/STI1 when bound to PrP. Differing from a recent dimeric model of human hop/STI1, both size-exclusion chromatography and SAXS data support a monomeric form of free murine hop/STI1. Changes in the PrP(143-153) alpha-helix may engage the transmembrane signaling proteins laminin receptor precursor and neural cell adhesion molecule, both of which bind that domain of PrPC, and further ligands may be engaged by the tertiary structural changes of hop/STI1. These reciprocal structural modifications indicate a versatile mechanism for signaling mediated by PrPC: hop/STI1 interaction, consistent with the hypothesis of PrPC-dependent multiprotein signaling complexes.-Romano, S. A., Cordeiro, Y., Lima, L. M. T. R., Lopes, M. H., Silva, J. L., Foguel, D., Linden, R. Reciprocal remodeling upon binding of the prion protein to its signaling partner hop/STI1. FASEB J. 23, 4308-4316 (2009). www.fasebj.org (AU)