ジャーナル: Sci Adv / 年: 2022 タイトル: Structural basis for HCMV Pentamer recognition by neuropilin 2 and neutralizing antibodies. 著者: Daniel Wrapp / Xiaohua Ye / Zhiqiang Ku / Hang Su / Harrison G Jones / Nianshuang Wang / Akaash K Mishra / Daniel C Freed / Fengsheng Li / Aimin Tang / Leike Li / Dabbu Kumar Jaijyan / Hua ...著者: Daniel Wrapp / Xiaohua Ye / Zhiqiang Ku / Hang Su / Harrison G Jones / Nianshuang Wang / Akaash K Mishra / Daniel C Freed / Fengsheng Li / Aimin Tang / Leike Li / Dabbu Kumar Jaijyan / Hua Zhu / Dai Wang / Tong-Ming Fu / Ningyan Zhang / Zhiqiang An / Jason S McLellan / 要旨: Human cytomegalovirus (HCMV) encodes multiple surface glycoprotein complexes to infect a variety of cell types. The HCMV Pentamer, composed of gH, gL, UL128, UL130, and UL131A, enhances entry into ...Human cytomegalovirus (HCMV) encodes multiple surface glycoprotein complexes to infect a variety of cell types. The HCMV Pentamer, composed of gH, gL, UL128, UL130, and UL131A, enhances entry into epithelial, endothelial, and myeloid cells by interacting with the cell surface receptor neuropilin 2 (NRP2). Despite the critical nature of this interaction, the molecular determinants that govern NRP2 recognition remain unclear. Here, we describe the cryo-EM structure of NRP2 bound to Pentamer. The high-affinity interaction between these proteins is calcium dependent and differs from the canonical carboxyl-terminal arginine (CendR) binding that NRP2 typically uses. We also determine the structures of four neutralizing human antibodies bound to the HCMV Pentamer to define susceptible epitopes. Two of these antibodies compete with NRP2 binding, but the two most potent antibodies recognize a previously unidentified epitope that does not overlap the NRP2-binding site. Collectively, these findings provide a structural basis for HCMV tropism and antibody-mediated neutralization.
全体 : The ectodomain of the HCMV pentamer bound by domains a1a2b1b2 of ...
全体
名称: The ectodomain of the HCMV pentamer bound by domains a1a2b1b2 of human neuropilin 2
要素
複合体: The ectodomain of the HCMV pentamer bound by domains a1a2b1b2 of human neuropilin 2
複合体: The ectodomain of the HCMV pentamer
タンパク質・ペプチド: Envelope protein UL128
タンパク質・ペプチド: Envelope glycoprotein UL130
タンパク質・ペプチド: UL131A
複合体: Domains a1a2b1b2 of human neuropilin 2
タンパク質・ペプチド: Neuropilin-2
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
リガンド: CALCIUM ION
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超分子 #1: The ectodomain of the HCMV pentamer bound by domains a1a2b1b2 of ...
超分子
名称: The ectodomain of the HCMV pentamer bound by domains a1a2b1b2 of human neuropilin 2 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 詳細: The primary map is the result of a focused refinement that encompasses the HCMV UL proteins (UL128, UL130, UL131) and NRP2 domains a2b1b2. The included additional map is the non-focused ...詳細: The primary map is the result of a focused refinement that encompasses the HCMV UL proteins (UL128, UL130, UL131) and NRP2 domains a2b1b2. The included additional map is the non-focused refinement in which the entire HCMV pentamer ectodomain and the entirety of NRP2 a1a2b1b2 can be observed.
分子量
理論値: 230 KDa
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超分子 #2: The ectodomain of the HCMV pentamer
超分子
名称: The ectodomain of the HCMV pentamer / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1-#3
由来(天然)
生物種: Human betaherpesvirus 5 (ヘルペスウイルス)
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超分子 #3: Domains a1a2b1b2 of human neuropilin 2
超分子
名称: Domains a1a2b1b2 of human neuropilin 2 / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #4