THE LYSINE GINGIPAIN ADHESIN DOMAINS FROM PORPHYROMONAS GINGIVALIS INTERACT WITH ERYTHROCYTES AND ALBUMIN: STRUCTURES CORRELATE TO FUNCTION
THE LYSINE GINGIPAIN ADHESIN DOMAINS FROM PORPHYROMONAS GINGIVALIS INTERACT WITH ERYTHROCYTES AND ALBUMIN: STRUCTURES CORRELATE TO FUNCTION
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DOI：
10.1556/eujmi.3.2013.3.2
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发表时间：
2013-09-01
影响因子：
2.2
通讯作者：
Collyer, C. A.
中科院分区：
文献类型：
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作者：
Ganuelas, L. A.;Li, N.;Collyer, C. A.
K1结构域的晶体结构，由牙周病厌氧菌牙龈卟啉单胞菌W83的细胞表面上表达的赖氨酸牙龈菌蛋白酶（Kgp）的粘附素模块，与先前确定的同源物K2和K3的结构进行比较，所有三个都是切割的粘附素结构域家族的代表性成员。在K1的结构中，最广泛的表面环的构象出乎意料地受到扰动，也许是晶体堆积，并从先前报道的K2和K3中观察到的精氨酸锚定位置移位。这种置换允许环自由地与其他蛋白质相互作用;交替翻转环构象是与靶宿主蛋白质、其他细菌或其他牙龈菌蛋白酶蛋白结构域相互作用的新机制。此外，K1粘附素模块，像其他模块一样，被发现在体外是溶血性的，因此，在红细胞识别中起作用，从而有助于Kgp的溶血功能。还观察到K1以高亲和力选择性地结合至血白蛋白，这表明该结构域可能参与牙龈卟啉菌蛋白酶介导的从血白蛋白的血红素获取。因此，最有可能的是Kgp的所有切割的粘附素结构域以比简单介导细菌粘附更复杂的方式促成牙龈卟啉单胞菌的致病性。
The crystal structure of the K1 domain, an adhesin module of the lysine gingipain (Kgp) expressed on the cell surface by the periodontopathic anaerobic bacterium, Porphyromonas gingivalis W83, is compared to the previously determined structures of homologues K2 and K3, all three being representative members of the cleaved adhesin domain family. In the structure of K1, the conformation of the most extensive surface loop is unexpectedly perturbed, perhaps by crystal packing, and is displaced from a previously reported arginine-anchored position observed in K2 and K3. This displacement allows the loop to become free to interact with other proteins; the alternate flipped-out loop conformation is a novel mechanism for interacting with target host proteins, other bacteria, or other gingipain protein domains. Further, the K1 adhesin module, like others, is found to be haemolytic in vitro, and so, functions in erythrocyte recognition thereby contributing to the haemolytic function of Kgp. K1 was also observed to selectively bind to haem-albumin with high affinity, suggesting this domain may be involved in gingipain-mediated haem acquisition from haem-albumin. Therefore, it is most likely that all cleaved adhesin domains of Kgp contribute to the pathogenicity of P. gingivalis in more complex ways than simply mediating bacterial adherence.