Plexin‑Bs enhance their GAP activity with a novel activation switch loop generating a cooperative enzyme.

Zhen-Lu Li, Jeannine Müller-Greven, Soonjeung Kim, Luca Tamagnone, Matthias Buck

Risultato della ricerca: Contributo in rivistaArticolo

Abstract

Plexins receive guidance cues from semaphorin ligands and transmit their signal through the plasma membrane. This family of proteins is unique amongst single-pass transmembrane receptors as their intracellular regions interact directly with several small GTPases, which regulate cytoskeletal dynamics and cell adhesion. Here, we characterize the GTPase Activating Protein (GAP) function of Plexin-B1 and fnd that a cooperative GAP activity towards the substrate GTPase, Rap1b, is associated with the N-terminal Juxtamembrane region of Plexin-B1. Importantly, we unveil an activation mechanism of Plexin-B1 by identifying a novel functional loop which partially blocks Rap1b entry into the plexin GAP domain. Consistent with the concept of allokairy developed for other systems, Plexin-B activity is increased by an apparent substrate-mediated cooperative efect. Simulations and mutagenesis suggest the repositioned JM conformation is stabilized by the new activation switch loop when the active site is occupied, giving rise to faster enzymatic turnover and cooperative behavior. The biological implications, essentially those of a threshold behavior for cell migration, are discussed
Lingua originaleInglese
pagine (da-a)1101-1112
Numero di pagine12
RivistaCellular and Molecular Life Sciences
Volume78
DOI
Stato di pubblicazionePubblicato - 2021

Keywords

  • ACTIVATION THRESHOLD
  • ALLOSTERY
  • CELL MIGRATION
  • CELL SIGNALING
  • MOLECULAR MECHANISM
  • SMALL GTPase

Fingerprint

Entra nei temi di ricerca di 'Plexin‑Bs enhance their GAP activity with a novel activation switch loop generating a cooperative enzyme.'. Insieme formano una fingerprint unica.

Cita questo