Background: FKBP38 regulates the biogenesis of plasma membrane ion channels. Results: FKBP38 inhibits protein synthesis through its membrane anchorage and promotes CFTR post-translational folding through its PPIase domain, both negatively regulated by Hsp90 through the tetratricopeptide repeat domain. Conclusion: FKBP38 PPIase plays an important role in CFTR biogenesis. Significance: Our findings demonstrate an independent contribution of FKBP38 to CFTR biogenesis.

No abstract

Background: Hsp105 prevents protein aggregation, accelerates Hsc70 nucleotide exchange, and functionally relates to Hsp90. Results: Hsp105 facilitates CFTR quality control coincident with translation, enhances its post-translational folding, and stabilizes misfolded CFTR at cell periphery. Conclusion: Hsp105 is a versatile regulator in CFTR folding and quality control. Significance: Hsp105 plays distinct roles in CFTR folding from other Hsc70 nucleotide exchange factors.

Most proteins comprise two or more domains from a limited suite of protein families. These domains are often rearranged in various combinations through gene fusion events to evolve new protein functions, including the acquisition of protein allostery through the incorporation of regulatory domains. The enzyme 3-deoxy-d--heptulosonate 7-phosphate synthase (DAH7PS) is the first enzyme of aromatic amino acid biosynthesis and displays a diverse range of allosteric mechanisms. DAH7PSs adopt a common architecture with a shared (β/α) catalytic domain which can be attached to an ACT-like or a chorismate mutase regulatory domain that operates via distinct mechanisms. These respective domains confer allosteric regulation by controlling DAH7PS function in response to ligand Tyr or prephenate. Starting with contemporary DAH7PS proteins, two protein chimeras were created, with interchanged regulatory domains. Both engineered proteins were catalytically active and delivered new functional allostery with switched ligand specificity and allosteric mechanisms delivered by their nonhomologous regulatory domains. This interchangeability of protein domains represents an efficient method not only to engineer allostery in multidomain proteins but to create a new bifunctional enzyme.

No abstract