A superfamily of proteins called Cysteine Transmembrane (CYSTM) is widely distributed across eukaryotes. These small proteins are characterized by the presence of a conserved motif at the C-terminal region, rich in cysteines, that has been annotated as a transmembrane domain. Orthologues of these proteins have been involved in resistance to pathogens and metal detoxification. The yeast members of the family are YBR016W, YDL012C, YDR034W-B, and YDR210W. Here we begin the characterization of these proteins at the molecular level and show that Ybr016w, Ydr034w-b, and Ydr210w are palmitoylated proteins. Protein S-acylation or palmitoylation, is a post-translational modification that consists of the addition of long-chain fatty acids to cysteine residues. We provide evidence that Ybr016w, Ydr210w and Ydr034w-b are localized to the Plasma membrane (PM) and exhibit varying degrees of polarity towards the daughter cell, which is dependent on endocytosis and recycling. We suggest the names CPP1, CPP2 and CPP3 (C-terminally Palmitoylated Protein) for YBR016W, YDR210W and YDR034W-B, respectively. We show that palmitoylation is responsible for the binding of these proteins to the membrane indicating that the CYSTM on these proteins is not a transmembrane domain. We propose renaming the C-terminal cysteine-rich domain as CYSPD (CYSTEINE-rich Palmitoylated Domain). Loss of the Palmitoyltransferase (PAT) Erf2 leads to partial degradation of Ybr016w (Cpp1), whereas in the absence of the PAT Akr1, members of this family are completely degraded. For Cpp1, we show that this degradation occurs via the proteasome, in an Rsp5-dependent manner, but is not exclusively due to a lack of Cpp1 palmitoylation.

• PMID: 38159851
• DOI full text
• PubMed
• PubTator

Reference Type

Journal Article

Authors

Giolito ML, Bigliani G, Meinero R, Taubas JV

Primary Lit For

Additional Lit For

Review For