Two functionally distinct HEATR5 protein complexes are defined by fast-evolving co-factors in yeast

Area of Science:

• Cell Biology
• Molecular Biology
• Structural Biology

Background:

• HEATR5 proteins are crucial for membrane traffic, interacting with adaptor protein complex-1 (AP1).
• The precise mechanisms by which HEATR5 proteins engage their rapidly evolving co-factors remain largely unelucidated.

Approach:

• Investigated the budding yeast HEATR5 protein, Laa1, utilizing biochemical analyses and structure predictions.
• Identified two distinct Laa1-containing complexes, differentiated by mutually exclusive binding partners Laa2 and Lft1.
• Examined the structural basis of Lft1 and Laa2 interactions with Laa1, despite limited sequence homology.

Key Points:

• Laa1 operates within two biochemically distinct complexes, involving Laa2 and the novel protein Lft1.
• Both Laa1 complexes are implicated in intra-Golgi recycling pathways.
• Only the Laa2-Laa1 complex demonstrates direct binding to AP1, influencing its cellular localization.

Conclusions:

• Elucidated a conserved, structurally similar mechanism for HEATR5 co-factor binding in yeast and humans.
• Demonstrated that Laa1 possesses functions beyond AP1 recruitment, expanding our understanding of its cellular roles.
• Provided mechanistic insights into HEATR5 protein interactions and their implications in membrane trafficking.