Shah Deepan S H, Joucla Gilles, Remaud-Simeon Magali, Russell Roy R B
Oral Biology, School of Dental Sciences, University of Newcastle, Newcastle upon Tyne NE2 4BW, United Kingdom.
J Bacteriol. 2004 Dec;186(24):8301-8. doi: 10.1128/JB.186.24.8301-8308.2004.
Glucansucrases of oral streptococci and Leuconostoc mesenteroides have a common pattern of structural organization and characteristically contain a domain with a series of tandem amino acid repeats in which certain residues are highly conserved, particularly aromatic amino acids and glycine. In some glucosyltransferases (GTFs) the repeat region has been identified as a glucan binding domain (GBD). Such GBDs are also found in several glucan binding proteins (GBP) of oral streptococci that do not have glucansucrase activity. Alignment of the amino acid sequences of 20 glucansucrases and GBP showed the widespread conservation of the 33-residue A repeat first identified in GtfI of Streptococcus downei. Site-directed mutagenesis of individual highly conserved residues in recombinant GBD of GtfI demonstrated the importance of the first tryptophan and the tyrosine-phenylalanine pair in the binding of dextran, as well as the essential contribution of a basic residue (arginine or lysine). A microplate binding assay was developed to measure the binding affinity of recombinant GBDs. GBD of GtfI was shown to be capable of binding glucans with predominantly alpha-1,3 or alpha-1,6 links, as well as alternating alpha-1,3 and alpha-1,6 links (alternan). Western blot experiments using biotinylated dextran or alternan as probes demonstrated a difference between the binding of streptococcal GTF and GBP and that of Leuconostoc glucansucrases. Experimental data and bioinformatics analysis showed that the A repeat motif is distinct from the 20-residue CW motif, which also has conserved aromatic amino acids and glycine and which occurs in the choline-binding proteins of Streptococcus pneumoniae and other organisms.
口腔链球菌和肠系膜明串珠菌的葡聚糖蔗糖酶具有共同的结构组织模式,其特征是含有一个具有一系列串联氨基酸重复序列的结构域,其中某些残基高度保守,特别是芳香族氨基酸和甘氨酸。在一些葡糖基转移酶(GTF)中,重复区域已被确定为葡聚糖结合结构域(GBD)。这种GBD也存在于一些没有葡聚糖蔗糖酶活性的口腔链球菌的葡聚糖结合蛋白(GBP)中。对20种葡聚糖蔗糖酶和GBP的氨基酸序列进行比对,结果显示在唐氏链球菌的GtfI中首次鉴定出的33个残基的A重复序列具有广泛的保守性。对GtfI重组GBD中各个高度保守的残基进行定点诱变,结果表明第一个色氨酸以及酪氨酸-苯丙氨酸对在葡聚糖结合中具有重要作用,同时一个碱性残基(精氨酸或赖氨酸)也起着关键作用。开发了一种微孔板结合试验来测量重组GBD的结合亲和力。结果表明,GtfI的GBD能够结合主要具有α-1,3或α-1,6连接以及交替的α-1,3和α-1,6连接(交替聚糖)的葡聚糖。使用生物素化葡聚糖或交替聚糖作为探针的蛋白质印迹实验表明,链球菌GTF和GBP的结合与肠系膜明串珠菌葡聚糖蔗糖酶的结合存在差异。实验数据和生物信息学分析表明,A重复基序与20个残基的CW基序不同,后者也具有保守的芳香族氨基酸和甘氨酸,并且存在于肺炎链球菌和其他生物体的胆碱结合蛋白中。