Journal of Structural Biology
Visualitza/Obre
2013_JSB_Neuropilin_scan.pdf (1,122Mb) (Accés restringit)
Sol·licita una còpia a l'autor
Què és aquest botó?
Aquest botó permet demanar una còpia d'un document restringit a l'autor. Es mostra quan:
- Disposem del correu electrònic de l'autor
- El document té una mida inferior a 20 Mb
- Es tracta d'un document d'accés restringit per decisió de l'autor o d'un document d'accés restringit per política de l'editorial
Estadístiques de LA Referencia / Recolecta
Inclou dades d'ús des de 2022
Cita com:
hdl:2117/19027
Tipus de documentArticle
Data publicació2013-02-24
Condicions d'accésAccés restringit per política de l'editorial
Llevat que s'hi indiqui el contrari, els
continguts d'aquesta obra estan subjectes a la llicència de Creative Commons
:
Reconeixement-NoComercial-SenseObraDerivada 3.0 Espanya
Abstract
Neuropilin-1 (NRP-1) is a hub receptor that plays an essential role in angiogenesis and vascular perme-
ability. It is over-expres sed in the new blood vessels grown by tumor cells and is a target for anti-tumor
treatment s. Peptides that expose the consensus sequence R/K/
XX
R/K at the C-terminus (
C-end rule
or
CendR
peptides) bind to NRP-1 and are internalized into the cell. We used peptide phage display binding
assays and molecular dynamics (MD) simulations to study the potential role of the central residues of
CendR
peptides in binding and activa tion of the NRP-1 receptor. The high stability of RPAR–receptor
domain complex stems from the formation of a characteristic pattern of three hydrogen bonds between
the peptide C-terminus and the residues in the NRP-1 loop III. Any changes in the peptide structure that
fail to preserve this triad result in a less-stable complex. We performed a systematic study of R
XX
R
mutants, where
X
= A/D/S/R/P, in order to test the effect of replacement of A or P on the binding capabil-
ities. Our results, both experimental and computational, show that RRAR, RDAR, RPDR, RPRR and RPPR are
capable of binding NRP-1. However, only RPPR and RPRR segments form an optimal organization around
loop III with low potential energy. In other analogs, the absence of these stabilizing interactions always
results in higher potential energy of the complexes. The binding of RPAR analogs does not guarantee
receptor activation; only stable complexes that are properly stabilized via loop III appear able to trigger
NRP-1 activati on
CitacióZanuy, D. [et al.]. Journal of Structural Biology. "Journal of structural biology", 24 Febrer 2013, vol. 182, p. 78-86.
ISSN1047-8477
Fitxers | Descripció | Mida | Format | Visualitza |
---|---|---|---|---|
2013_JSB_Neuropilin_scan.pdf | 1,122Mb | Accés restringit |