Studies of YlxM of Streptococcus mutans, a newly identified component of the Sign

描述（由申请人提供）：膜用于描绘活细胞的边界，结合到膜中的蛋白质有助于定义其生物学功能。细菌膜蛋白的相关性可以通过以下事实来例证：近三分之一的细菌蛋白是与膜相关的或分泌的。变形链球菌是一种致龋口腔病原体，其毒力在很大程度上取决于其膜的组成。人类龋齿是一种普遍存在的传染病，占工业化国家医疗保健支出的5-10%。突变链球菌的信号识别颗粒（Signal Recognition Particle， SRP）通路在其膜生物发生和发病机制中起着重要作用。进一步了解这一途径对于理解变形链球菌毒力因子进入或穿过细胞质膜的基本潜在机制是必要的。突变S. mutans SRP突变体表现出生长缺陷，不能抵抗酸、渗透或氧化应激，并在小鼠模型中表现出显著降低的致癌性。SRP通路是一种在所有活细胞中保守的共翻译蛋白易位系统。在细菌中，有三种保守的成分被识别：Ffh，一种具有GTP水解（GTP酶）活性的蛋白质，可以结合新生多肽；FtsY，一种膜结合受体，结合Ffh并帮助将新生肽靶向到易位通道；以及参与Ffh-FtsY稳定性和催化GTPase活性的细胞质小RNA （scRNA）。本研究将研究YlxM，这是一种以前未被发现的蛋白，其基因在变形链球菌和其他革兰氏阳性和一些革兰氏阴性菌的ffh上游被发现。根据本申请中提供的初步数据，假设YlxM代表S. mutans SRP途径的另一个组成部分。本文提出了三个目标：1)确定YlxM与Ffh的相互作用并进行表征；2)确认并表征YlxM与scRNA的相互作用；3)评价YlxM对SRP通路组分功能的影响。这项研究支持NIDCR的目标，即研究龋齿生物，以确定导致龋齿过程的基因和途径。此外，这项研究代表了博士论文项目的基础。因此，这项奖学金申请将有助于培养对口腔健康研究感兴趣的学生成为一名独立的研究者。

DESCRIPTION (provided by applicant): Membranes serve to delineate the boundaries of living cells and proteins incorporated into membranes help to define their biological functions. The relevance of bacterial membrane proteins is exemplified by the fact that nearly a third of all bacterial proteins produced are membrane-associated or secreted. Streptococcus mutans is a cariogenic oral pathogen whose virulence is determined in large part by its membrane composition. Human dental caries is a ubiquitous infectious disease that represents 5-10% of healthcare expenditures in industrialized nations. The Signal Recognition Particle (SRP) pathway of Streptococcus mutans is known to play an important role in its membrane biogenesis and pathogenesis. A further understanding of this pathway is necessary to understand the basic underlying machinery by which S. mutans virulence factors get into or through the cytoplasmic membrane. S. mutans SRP mutants demonstrate growth defects, are unable to contend with acid, osmotic, or oxidative stress, and demonstrate significantly decreased cariogenicity in a murine model. The SRP pathway is a co-translational protein translocation system that is conserved in all living cells. In bacteria three conserved components are recognized: Ffh, a protein with GTP hydrolysis (GTPase) activity that binds nascent polypeptides; FtsY, a membrane bound receptor that binds Ffh and helps target nascent peptides to the translocon channel; and a small cytoplasmic RNA (scRNA) that is involved in the stability of Ffh-FtsY and catalysis of GTPase activity. This proposal will investigate YlxM, a previously uncharacterized protein whose gene is found immediately upstream of ffh in S. mutans and other Gram- positive and some Gram-negative organisms. Based on preliminary data presented in this application YlxM is hypothesized to represent an additional component of the S. mutans SRP pathway. Three aims are proposed: 1) To confirm and characterize the interaction of YlxM with Ffh; 2) To confirm and characterize the interaction of YlxM with the scRNA; and 3) Evaluate the influence of YlxM on the function of SRP pathway components. This research supports the NIDCR goal to investigate cariogenic organisms to identify genes and pathways that contribute to the decay process. Additionally this research represents the basis of a doctoral dissertation project. Hence, this fellowship application will assist in trainin a student with an interest in oral health research to become an independent investigator.