RT Journal Article
T1 The human VGF-derived bioactive peptide TLQP-21 binds heat shock 71 kDa protein 8 (HSPA8) on the surface of SH-SY5Y cells
A1 Akhter, Shamim
A1 Chakrabort, Sandipan
A1 Mesquita Moutinho, Daniela
A1 Álvarez Coiradas, Elia
A1 Rosa, Isaac
A1 Viñuela Roldán, Juan Evaristo
A1 Domínguez Medina, Eduardo
A1 García Alonso, Ángel
A1 Rodríguez Requena, Jesús
K1 Heat shock response
K1 Cell membranes
K1 Cell binding
K1 Hydrogen bonding
K1 Molecular dynamics
K1 Signal peptides
K1 Complement receptors
K1 Cross-linking
AB VGF (non-acronymic)is a secreted chromogranin/secretogranin that gives rise to a number of bioactive peptides by a complex proteolysis mechanism. VGF-derived peptides exert an extensive array of biological effects in energy metabolism, mood regulation, pain, gastric secretion function, reproduction and, perhaps, cancer. It is therefore surprising that very little is known about receptors and binding partners of VGF-derived peptides and their downstream molecular mechanisms of action. Here, using affinity chromatography and mass spectrometry-based protein identification, we have identified the heat shock cognate 71 kDa protein A8 (HSPA8)as a binding partner of human TLQP-21 on the surface of human neuroblastomaSH-SY5Y cells. Binding of TLQP-21 to membrane associated HSPA8 in live SH-SY5Y cells was further supported by cross-linking to live cells. Interaction between HSPA8 and TLQP-21 was confirmed in vitro by label-free Dynamic Mass Redistribution (DMR) studies. Furthermore, molecular modeling studies show that TLQP-21 can be docked into the HSPA8 peptide binding pocket. Identification of HSPA8 as a cell surface binding partner of TLQP-21 opens new avenues to explore the molecular mechanisms of its physiological actions, and of pharmacological modulation thereof.
PB PLOS
YR 2017
FD 2017
LK http://hdl.handle.net/10347/22918
UL http://hdl.handle.net/10347/22918
LA eng
NO Akhter S, Chakraborty S, Moutinho D, Álvarez-Coiradas E, Rosa I, Viñuela J, et al. (2017) The human VGF-derived bioactive peptide TLQP-21 binds heat shock 71 kDa protein 8 (HSPA8)on the surface of SH-SY5Y cells. PLoS ONE 12(9): e0185176. https://doi.org/10.1371/journal.pone.0185176
NO This work was supported by ERANETNEURON grant DISCover through the Spanishfunding partner Instituto de Salud Carlos III (www.isciii.es), grant: PI09/2688 to JRR
DS Minerva
RD 3 may 2026