腫瘍ヘルペスウイルスKSHVにおけるDNA包装ポータルおよびカプシド関連テグメント複合体

Danyang Gong¹, Xinghong Dai², Jonathan Jih³

¹Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Cell

|August 27, 2019

まとめ

カポシ

科学分野:

構造生物学
ウイルス学
分子生物学

背景:

カポシの肉腫関連ヘルペスウイルス (KSHV) の構成は複雑で,ポータル複合体,イコサヘドラルカプシド,カプシド関連テグメント複合体 (CATC) が含まれる.
以前の研究は,イコサヘドール対称性からの偏差によるKSHVの門との構造の解明に限られていた.

研究の目的:

KSHVポータル複合体の局所構造とウイルス成分との相互作用を決定する.
KSHVのプロカプシド形成とDNA包装のメカニズムを解明する.

主な方法:

シンメトリ・リラクゼッド・クライオ・電子顕微鏡 (Cryo-EM)
原子モデリング
構造に基づく変異性

主要な成果:

この研究では,KSHVポータルの原子構造とカプシドタンパク質,CATC,およびウイルスのdsDNAゲノムとの相互作用を決定した.
CATCの変数占有と方向性は観察され,DNA包装の際にアタッチメントの非対称的な決定に役割を果たすことを示唆しました.
CATCのトリプレックスに深く結合する溝が潜在的な抗ウイルス標的として特定されました.

結論:

KSHVポータルは,DNA包装中にプロカプシド形成とCATCの結合をオーケストラします.
特定されたCATC結合部位は,KSHVに対する新しい抗ウイルス療法の開発の有望なターゲットです.

キーワード:

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