A shared binding interface controls Vps13 organelle-specific targeting independently of its vacuolar protein sorting...

Area of Science:

• Cell biology
• Molecular mechanisms of protein transport
• Lipid dynamics

Background:

• Yeast vacuolar protein sorting 13 (Vps13) is a crucial transporter for inter-organelle lipid flow.
• Vps13 localization depends on organelle-specific adaptors that bind to the Vps13 adaptor-binding (VAB) domain, often via proline-X-proline (PxP) motifs.

Purpose of the Study:

• To investigate the binding mechanisms of Vps13 adaptors.
• To determine if the VAB-PxP interface is universally used by all Vps13 adaptors.
• To explore Vps13 function in the VPS pathway independent of PxP adaptors.

Main Methods:

• In vivo studies involving mutations in the VAB domain.
• Predictive modeling to analyze adaptor-Vps13 interactions.
• Functional assays for the VPS pathway.

Main Results:

• Mutations in the VAB-PxP interface disrupt adaptor binding and Vps13 membrane targeting.
• Predictive modeling suggests subtle interface differences drive adaptor competition.
• The VPS pathway operates independently of the PxP motif binding site, indicating a non-PxP adaptor mechanism.

Conclusions:

• The Vps13 adaptor-binding interface is critical for Vps13 function.
• Vps13 utilizes both PxP-dependent and potentially PxP-independent adaptor mechanisms.
• The VAB domain's structural integrity is essential for Vps13-mediated vacuolar protein sorting.