4F2H

Structure of the minimal Ste5 VWA domain subject to autoinhibition by the Ste5 PH domain

Summary for 4F2H

• Entry DOI: 10.2210/pdb4f2h/pdb
• Descriptor: Protein STE5 (1 entity in total)
• Functional Keywords: von wildebrand type a, ste5ms, coactivation of fus3, signaling protein
• Biological source: Saccharomyces cerevisiae (yeast)
• Cellular location: Cytoplasm: P32917
• Total number of polymer chains: 1
• Total formula weight: 23683.57

Authors

Coyle, S.M.,Zalatan, J.G.,Lim, W.A. (deposition date: 2012-05-07, release date: 2012-08-22, Last modification date: 2023-09-13)

Primary citation

Zalatan, J.G.,Coyle, S.M.,Rajan, S.,Sidhu, S.S.,Lim, W.A.
Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation.
Science, 337:1218-1222, 2012

PubMed Abstract: Cells reuse signaling proteins in multiple pathways, raising the potential for improper cross talk. Scaffold proteins are thought to insulate against such miscommunication by sequestering proteins into distinct physical complexes. We show that the scaffold protein Ste5, which organizes the yeast mating mitogen-activated protein kinase (MAPK) pathway, does not use sequestration to prevent misactivation of the mating response. Instead, Ste5 appears to use a conformation mechanism: Under basal conditions, an intramolecular interaction of the pleckstrin homology (PH) domain with the von Willebrand type A (VWA) domain blocks the ability to coactivate the mating-specific MAPK Fus3. Pheromone-induced membrane binding of Ste5 triggers release of this autoinhibition. Thus, in addition to serving as a conduit guiding kinase communication, Ste5 directly receives input information to decide if and when signal can be transmitted to mating output.

PubMed: 22878499
DOI: 10.1126/science.1220683

Experimental method

X-RAY DIFFRACTION (3.192 Å)