Skip to main content

Restricted substrate specificity for the geranylgeranyltransferase-I enzyme in Cryptococcus neoformans: implications for virulence.

Publication ,  Journal Article
Selvig, K; Ballou, ER; Nichols, CB; Alspaugh, JA
Published in: Eukaryot Cell
November 2013

Proper cellular localization is required for the function of many proteins. The CaaX prenyltransferases (where CaaX indicates a cysteine followed by two aliphatic amino acids and a variable amino acid) direct the subcellular localization of a large group of proteins by catalyzing the attachment of hydrophobic isoprenoid moieties onto C-terminal CaaX motifs, thus facilitating membrane association. This group of enzymes includes farnesyltransferase (Ftase) and geranylgeranyltransferase-I (Ggtase-1). Classically, the variable (X) amino acid determines whether a protein will be an Ftase or Ggtase-I substrate, with Ggtase-I substrates often containing CaaL motifs. In this study, we identify the gene encoding the β subunit of Ggtase-I (CDC43) and demonstrate that Ggtase-mediated activity is not essential. However, Cryptococcus neoformans CDC43 is important for thermotolerance, morphogenesis, and virulence. We find that Ggtase-I function is required for full membrane localization of Rho10 and the two Cdc42 paralogs (Cdc42 and Cdc420). Interestingly, the related Rac and Ras proteins are not mislocalized in the cdc43Δ mutant even though they contain similar CaaL motifs. Additionally, the membrane localization of each of these GTPases is dependent on the prenylation of the CaaX cysteine. These results indicate that C. neoformans CaaX prenyltransferases may recognize their substrates in a unique manner from existing models of prenyltransferase specificity. It also suggests that the C. neoformans Ftase, which has been shown to be more important for C. neoformans proliferation and viability, may be the primary prenyltransferase for proteins that are typically geranylgeranylated in other species.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Eukaryot Cell

DOI

EISSN

1535-9786

Publication Date

November 2013

Volume

12

Issue

11

Start / End Page

1462 / 1471

Location

United States

Related Subject Headings

  • Virulence
  • Substrate Specificity
  • Protein Prenylation
  • Microbiology
  • Fungal Proteins
  • Dimethylallyltranstransferase
  • Cryptococcus neoformans
  • Cell Cycle Proteins
  • Alkyl and Aryl Transferases
  • 3107 Microbiology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Selvig, K., Ballou, E. R., Nichols, C. B., & Alspaugh, J. A. (2013). Restricted substrate specificity for the geranylgeranyltransferase-I enzyme in Cryptococcus neoformans: implications for virulence. Eukaryot Cell, 12(11), 1462–1471. https://doi.org/10.1128/EC.00193-13
Selvig, Kyla, Elizabeth R. Ballou, Connie B. Nichols, and J Andrew Alspaugh. “Restricted substrate specificity for the geranylgeranyltransferase-I enzyme in Cryptococcus neoformans: implications for virulence.Eukaryot Cell 12, no. 11 (November 2013): 1462–71. https://doi.org/10.1128/EC.00193-13.
Selvig K, Ballou ER, Nichols CB, Alspaugh JA. Restricted substrate specificity for the geranylgeranyltransferase-I enzyme in Cryptococcus neoformans: implications for virulence. Eukaryot Cell. 2013 Nov;12(11):1462–71.
Selvig, Kyla, et al. “Restricted substrate specificity for the geranylgeranyltransferase-I enzyme in Cryptococcus neoformans: implications for virulence.Eukaryot Cell, vol. 12, no. 11, Nov. 2013, pp. 1462–71. Pubmed, doi:10.1128/EC.00193-13.
Selvig K, Ballou ER, Nichols CB, Alspaugh JA. Restricted substrate specificity for the geranylgeranyltransferase-I enzyme in Cryptococcus neoformans: implications for virulence. Eukaryot Cell. 2013 Nov;12(11):1462–1471.

Published In

Eukaryot Cell

DOI

EISSN

1535-9786

Publication Date

November 2013

Volume

12

Issue

11

Start / End Page

1462 / 1471

Location

United States

Related Subject Headings

  • Virulence
  • Substrate Specificity
  • Protein Prenylation
  • Microbiology
  • Fungal Proteins
  • Dimethylallyltranstransferase
  • Cryptococcus neoformans
  • Cell Cycle Proteins
  • Alkyl and Aryl Transferases
  • 3107 Microbiology