Structure of adenovirus complexed with its internalization receptor, αvβ5 integrin
Structure of adenovirus complexed with its internalization receptor, αvβ5 integrin
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DOI：
10.1128/jvi.73.8.6759-6768.1999
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发表时间：
1999-08-01
影响因子：
5.4
通讯作者：
Stewart, PL
中科院分区：
文献类型：
--
作者：
Chiu, CY;Mathias, P;Stewart, PL
已通过冷冻电子显微镜（cryo-EM）以类似于21埃的分辨率测定了与人2型和12型腺病毒（Ad 2和-12）结合的可溶性重组整合素α（v）β 5的三维结构。已知α（v）β 5整联蛋白可促进Ad细胞进入。Cryo-EM已经显示Ad 2五邻体基础蛋白的整合素结合RGD（Arg-Gly-Asp）突起是高度移动的（P.L.斯图尔特角，澳-地Y.邱，S。Huang，T.黄氏叶蝉Muir，Y. Zhao，B. Chait，P. Mathias，and G. R. Nemerow，EMBO J. 16：1189-1198，1997）。序列分析表明，Ad 12 RGD表面环比Ad 2的表面环更短，并且可能柔性较差，因此更适合于Ad-整联蛋白复合物的结构表征。两种病毒-受体复合物的冷冻-EM结构揭示了每种病毒血清型的五邻体基底上方的整联蛋白密度环。正如预期的那样，Ad 2复合物中的整合素密度是弥散的，而Ad 12复合物中的整合素密度更好地定义。整联蛋白由两个离散的亚结构域组成，一个是具有直径类似于20埃的RGD结合裂缝的球状结构域，另一个是具有延伸的柔性尾部的远端结构域。Ad 2与α（v）β 5相互作用的动力学分析表明，在接近饱和时，每个五邻体碱基结合的整合素分子类似于4.2个。这些结果表明，五邻体上五个RGD突起的精确空间排列促进了整合素聚集和病毒内化所需的信号事件。
The three-dimensional structure of soluble recombinant integrin alpha(v)beta 5 bound to human adenovirus types 2 and 12 (Ad2 and -12) has been determined at similar to 21-Angstrom resolution by cryoelectron microscopy (cryo-EM). The alpha(v)beta 5 integrin is known to promote Ad cell entry. Cryo-EM has shown that the integrin-binding RGD (Arg-Gly-Asp) protrusion of the Ad2 penton base protein is highly mobile (P. L. Stewart, C. Y. Chiu, S. Huang, T. Muir, Y. Zhao, B. Chait, P. Mathias, and G. R. Nemerow, EMBO J. 16:1189-1198, 1997). Sequence analysis indicated that the Ad12 RGD surface loop is shorter than that of Ad2 and probably less flexible, hence more suitable for structural characterization of the Ad-integrin complex. The cryo-EM structures of the two virus-receptor complexes revealed a ring of integrin density above the penton base of each virus serotype. As expected, the integrin density in the Ad2 complex was diffuse while that in the Ad12 complex was better defined. The integrin consists of two discrete subdomains, a globular domain with an RGD-binding cleft similar to 20 Angstrom in diameter and a distal domain with extended, flexible tails. Kinetic analysis of Ad2 interactions with alpha(v)beta 5 indicated similar to 4.2 integrin molecules bound per penton base at close to saturation. These results suggest that the precise spatial arrangement of five RGD protrusions on the penton base promotes integrin clustering and the signaling events required for virus internalization.