Coiled-coil irregularities and instabilities in group A Streptococcus M1 are required for virulence

被引：124

作者：

McNamara, Case ^{[1
]}

Zinkernagel, Annelies S. ^{[2
]}

Macheboeuf, Pauline ^{[1
]}

Cunningham, Madeleine W. ^{[3
]}

Nizet, Victor ^{[2
,4
]}

Ghosh, Partho ^{[1
,5
]}

机构：

[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA

[3] Univ Oklahoma, Hlth Sci Ctr, Biomed Res Ctr, Oklahoma City, OK 73104 USA

[4] Univ Calif San Diego, Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Mol Biol Sect, La Jolla, CA 92093 USA

来源：

SCIENCE | 2008年 / 319卷 / 5868期

关键词：

D O I：

10.1126/science.1154470

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus ( GAS). Here, we report the similar to 3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type- specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross- reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross- reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.

引用

页码：1405 / 1408

页数：4

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