Global Analysis of Protein Palmitoylation in Yeast

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2006 Jun 6

PMID 16751107

Citations 275

Authors

Amy F Roth

Junmei Wan

Aaron O Bailey

Beimeng Sun

Jason A Kuchar

William N Green

Brett S Phinney

John R Yates 3rd

Nicholas G Davis

Affiliations

Soon will be listed here.

Abstract

Protein palmitoylation is a reversible lipid modification that regulates membrane tethering for key proteins in cell signaling, cancer, neuronal transmission, and membrane trafficking. Palmitoylation has proven to be a difficult study: Specifying consensuses for predicting palmitoylation remain unavailable, and first-example palmitoylation enzymes--i.e., protein acyltransferases (PATs)--were identified only recently. Here, we use a new proteomic methodology that purifies and identifies palmitoylated proteins to characterize the palmitoyl proteome of the yeast Saccharomyces cerevisiae. Thirty-five new palmitoyl proteins are identified, including many SNARE proteins and amino acid permeases as well as many other participants in cellular signaling and membrane trafficking. Analysis of mutant yeast strains defective for members of the DHHC protein family, a putative PAT family, allows a matching of substrate palmitoyl proteins to modifying PATs and reveals the DHHC family to be a family of diverse PAT specificities responsible for most of the palmitoylation within the cell.

Citing Articles

Defining proteoform-specific interactions for drug targeting in a native cell signalling environment.

Lutomski C, Bennett J, El-Baba T, Wu D, Hinkle J, Burnap S Nat Chem. 2025; 17(2):204-214.

PMID: 39806141 PMC: 11794133. DOI: 10.1038/s41557-024-01711-w.

Bioinformatics and Expression Profiling of the DHHC-CRD S-Acyltransferases Reveal Their Roles in Growth and Stress Response in Woodland Strawberry ().

Gu S, Nie X, George A, Tyler K, Xing Y, Qin L Plants (Basel). 2025; 14(1.

PMID: 39795387 PMC: 11722789. DOI: 10.3390/plants14010127.

Recapitulating the potential contribution of protein S-palmitoylation in cancer.

Chaturvedi S, Sonawane A Cancer Metastasis Rev. 2024; 44(1):20.

PMID: 39725785 DOI: 10.1007/s10555-024-10217-3.

Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders.

Wlodarczyk J, Bhattacharyya R, Dore K, Ho G, Martin D, Mejias R J Neurosci. 2024; 44(40).

PMID: 39358031 PMC: 11450541. DOI: 10.1523/JNEUROSCI.1225-24.2024.

Post-translational modifications in the Protein Data Bank.

Schofield L, Dialpuri J, Murshudov G, Agirre J Acta Crystallogr D Struct Biol. 2024; 80(Pt 9):647-660.

PMID: 39207896 PMC: 11394121. DOI: 10.1107/S2059798324007794.

References

Dietrich L, Gurezka R, Veit M, Ungermann C . The SNARE Ykt6 mediates protein palmitoylation during an early stage of homotypic vacuole fusion. EMBO J. 2003; 23(1):45-53. PMC: 1271655. DOI: 10.1038/sj.emboj.7600015. View

LINK A, Eng J, Schieltz D, Carmack E, Mize G, Morris D . Direct analysis of protein complexes using mass spectrometry. Nat Biotechnol. 1999; 17(7):676-82. DOI: 10.1038/10890. View

Couve A, Protopopov V, Gerst J . Yeast synaptobrevin homologs are modified posttranslationally by the addition of palmitate. Proc Natl Acad Sci U S A. 1995; 92(13):5987-91. PMC: 41627. DOI: 10.1073/pnas.92.13.5987. View

Brown D, London E . Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol. 1999; 14:111-36. DOI: 10.1146/annurev.cellbio.14.1.111. View

Wedegaertner P, Bourne H . Activation and depalmitoylation of Gs alpha. Cell. 1994; 77(7):1063-70. DOI: 10.1016/0092-8674(94)90445-6. View

El-Husseini A, Schnell E, Dakoji S, Sweeney N, Zhou Q, Prange O . Synaptic strength regulated by palmitate cycling on PSD-95. Cell. 2002; 108(6):849-63. DOI: 10.1016/s0092-8674(02)00683-9. View

Lobo S, Greentree W, Linder M, Deschenes R . Identification of a Ras palmitoyltransferase in Saccharomyces cerevisiae. J Biol Chem. 2002; 277(43):41268-73. DOI: 10.1074/jbc.M206573200. View

Tu Y, Wang J, Ross E . Inhibition of brain Gz GAP and other RGS proteins by palmitoylation of G protein alpha subunits. Science. 1997; 278(5340):1132-5. DOI: 10.1126/science.278.5340.1132. View

BARTELS D, Mitchell D, Dong X, Deschenes R . Erf2, a novel gene product that affects the localization and palmitoylation of Ras2 in Saccharomyces cerevisiae. Mol Cell Biol. 1999; 19(10):6775-87. PMC: 84674. DOI: 10.1128/MCB.19.10.6775. View

10.

Turnbull A, Kummel D, Prinz B, Holz C, Schultchen J, Lang C . Structure of palmitoylated BET3: insights into TRAPP complex assembly and membrane localization. EMBO J. 2005; 24(5):875-84. PMC: 554119. DOI: 10.1038/sj.emboj.7600565. View

11.

Ghaemmaghami S, Huh W, Bower K, Howson R, Belle A, Dephoure N . Global analysis of protein expression in yeast. Nature. 2003; 425(6959):737-41. DOI: 10.1038/nature02046. View

12.

Fukata M, Fukata Y, Adesnik H, Nicoll R, Bredt D . Identification of PSD-95 palmitoylating enzymes. Neuron. 2004; 44(6):987-96. DOI: 10.1016/j.neuron.2004.12.005. View

13.

Kihara A, Kurotsu F, Sano T, Iwaki S, Igarashi Y . Long-chain base kinase Lcb4 Is anchored to the membrane through its palmitoylation by Akr1. Mol Cell Biol. 2005; 25(21):9189-97. PMC: 1265802. DOI: 10.1128/MCB.25.21.9189-9197.2005. View

14.

Bock J, Matern H, Peden A, Scheller R . A genomic perspective on membrane compartment organization. Nature. 2001; 409(6822):839-41. DOI: 10.1038/35057024. View

15.

Ihara K, Muraguchi S, Kato M, Shimizu T, Shirakawa M, Kuroda S . Crystal structure of human RhoA in a dominantly active form complexed with a GTP analogue. J Biol Chem. 1998; 273(16):9656-66. DOI: 10.1074/jbc.273.16.9656. View

16.

Resh M . Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta. 1999; 1451(1):1-16. DOI: 10.1016/s0167-4889(99)00075-0. View

17.

Roth A, Feng Y, Chen L, Davis N . The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase. J Cell Biol. 2002; 159(1):23-8. PMC: 2173492. DOI: 10.1083/jcb.200206120. View

18.

Panek H, Stepp J, ENGLE H, Marks K, Tan P, Lemmon S . Suppressors of YCK-encoded yeast casein kinase 1 deficiency define the four subunits of a novel clathrin AP-like complex. EMBO J. 1997; 16(14):4194-204. PMC: 1170045. DOI: 10.1093/emboj/16.14.4194. View

19.

Huang K, Yanai A, Kang R, Arstikaitis P, Singaraja R, Metzler M . Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins. Neuron. 2004; 44(6):977-86. DOI: 10.1016/j.neuron.2004.11.027. View

20.

Dietrich L, Peplowska K, LaGrassa T, Hou H, Rohde J, Ungermann C . The SNARE Ykt6 is released from yeast vacuoles during an early stage of fusion. EMBO Rep. 2005; 6(3):245-50. PMC: 1299260. DOI: 10.1038/sj.embor.7400350. View