Evolutionary divergence of an elongation factor 3 from Cryptococcus neoformans

被引:11
作者
Blakely, G
Hekman, J
Chakraburtty, K
Williamson, PR
机构
[1] Univ Illinois, Coll Med, Div Infect Dis, Chicago, IL 60612 USA
[2] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA
关键词
D O I
10.1128/JB.183.7.2241-2248.2001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Elongation factor 3 (EF3) is considered a promising drug target for the control of fungal diseases because of its requirement for protein synthesis and survival of fungi and a lack of EF3 in the mammalian host. However, EF3 has been characterized only in ascomycete yeast. In order to understand the role of EF3 in a basidiomycete yeast, we cloned the gene encoding EF3 from Cryptococcus neoformans (CnEF3), an important fungal pathogen in immunocompromised patients, including those infected with human immunodeficiency virus. CnEF3 was found to encode a 1,055-amino-acid protein and has 44% identity with EP3 from Saccharomyces cerevisiae (YEF3). Expressed CnEF3 exhibited ATPase activity that,vas only modestly stimulated by ribosomes from S. cerevisiae. In contrast, CnEF3 showed tight binding to cryptococcal ribosomes, as shown by an inability to be removed under conditions which successfully remove Saccharomyces EF3 from ribosomes (0.5 M KCl or 2 M LiCl). CnEF3 also poorly complemented a YEF3 defect in a diploid null mutant and two temperature-sensitive mutants which have been shown previously to be complemented well by EF3 from other ascomycetes, such as Candida albicans. These data clearly identify the presence of a functioning EF3 in the basidiomycete yeast C. neoformans, which demonstrates an evolutionary divergence from EF3 of ascomycete yeast.
引用
收藏
页码:2241 / 2248
页数:8
相关论文
共 34 条
[1]   USE OF AMPHOTERICIN-B IN MAN [J].
ANDRIOLE, VT ;
KRAVETZ, HM .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1962, 180 (04) :269-&
[2]   SUSCEPTIBILITIES OF SERIAL CRYPTOCOCCUS-NEOFORMANS ISOLATES FROM PATIENTS WITH RECURRENT CRYPTOCOCCAL MENINGITIS TO AMPHOTERICIN-B AND FLUCONAZOLE [J].
CASADEVALL, A ;
SPITZER, ED ;
WEBB, D ;
RINALDI, MG .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1993, 37 (06) :1383-1386
[3]  
Casadevall A, 1998, CRYPTOCOCCUS NEOFORM, DOI DOI 10.1128/9781555818241
[4]   Yeast elongation factor 3: Structure and function [J].
Chakraburtty, K ;
Triana-Alonso, FJ .
BIOLOGICAL CHEMISTRY, 1998, 379 (07) :831-840
[5]   ELONGATION-FACTOR-3 (EF-3) FROM CANDIDA-ALBICANS SHOWS BOTH STRUCTURAL AND FUNCTIONAL SIMILARITY TO EF-3 FROM SACCHAROMYCES-CEREVISIAE [J].
COLTHURST, DR ;
SCHAUDER, BS ;
HAYES, MV ;
TUITE, MF .
MOLECULAR MICROBIOLOGY, 1992, 6 (08) :1025-1033
[6]  
COLTHURST DR, 1991, FEMS MICROBIOL LETT, V80, P45, DOI 10.1111/j.1574-6968.1991.tb04634.x
[7]  
DASMAHAPATRA B, 1981, J BIOL CHEM, V256, P9999
[8]   ISOLATION AND SEQUENCE-ANALYSIS OF THE GENE ENCODING TRANSLATION ELONGATION FACTOR-III FROM CANDIDA-ALBICANS [J].
DIDOMENICO, BJ ;
LUPISELLA, J ;
SANDBAKEN, M ;
CHAKRABURTTY, K .
YEAST, 1992, 8 (05) :337-352
[9]   Phenotypic switching in the human pathogenic fungus Cryptococcus neoformans is associated with changes in virulence and pulmonary inflammatory response in rodents [J].
Goldman, DL ;
Fries, BC ;
Franzot, SP ;
Montella, L ;
Casadevall, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14967-14972
[10]   The N terminus of eukaryotic translation elongation factor 3 interacts with 18 S rRNA and 80 S ribosomes [J].
Gontarek, RR ;
Li, H ;
Nurse, K ;
Prescott, CD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (17) :10249-10252