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-Structure paper
タイトル | Affinity-matured homotypic interactions induce spectrum of PfCSP structures that influence protection from malaria infection. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 4546, Year 2023 |
掲載日 | 2023年7月28日 |
著者 | Gregory M Martin / Jonathan L Torres / Tossapol Pholcharee / David Oyen / Yevel Flores-Garcia / Grace Gibson / Re'em Moskovitz / Nathan Beutler / Diana D Jung / Jeffrey Copps / Wen-Hsin Lee / Gonzalo Gonzalez-Paez / Daniel Emerling / Randall S MacGill / Emily Locke / C Richter King / Fidel Zavala / Ian A Wilson / Andrew B Ward / |
PubMed 要旨 | The generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an ...The generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an effective malaria vaccine. Here we present an in-depth structural and functional analysis of a panel of potent antibodies encoded by the immunoglobulin heavy chain variable (IGHV) gene IGHV3-33, which is among the most prevalent and potent antibody families induced in the anti-PfCSP immune response and targets the Asn-Ala-Asn-Pro (NANP) repeat region. Cryo-electron microscopy (cryo-EM) reveals a remarkable spectrum of helical antibody-PfCSP structures stabilized by homotypic interactions between tightly packed fragments antigen binding (Fabs), many of which correlate with somatic hypermutation. We demonstrate a key role of these mutated homotypic contacts for high avidity binding to PfCSP and in protection from Pf malaria infection. Together, these data emphasize the importance of anti-homotypic affinity maturation in the frequent selection of IGHV3-33 antibodies and highlight key features underlying the potent protection of this antibody family. |
リンク | Nat Commun / PubMed:37507365 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.9 - 3.84 Å |
構造データ | EMDB-27781, PDB-8dyt: EMDB-27784, PDB-8dyw: EMDB-27785, PDB-8dyx: EMDB-27786, PDB-8dyy: EMDB-27787, PDB-8dz3: EMDB-27788, PDB-8dz4: EMDB-27789, PDB-8dz5: PDB-8ekf: |
化合物 | ChemComp-HOH: |
由来 |
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キーワード | IMMUNE SYSTEM / malaria antibody / PfCSP / Antibody / Antigen / Malaria |