1TUE

The X-ray Structure of the Papillomavirus Helicase in Complex with its Molecular Matchmaker E2

1TUE の概要

• エントリーDOI: 10.2210/pdb1tue/pdb
• 分子名称: Replication protein E1, Regulatory protein E2 (3 entities in total)
• 機能のキーワード: human papillomavirus, helicase, replication, e1e2 complex, aaa+ protein
• 由来する生物種: Human papillomavirus type 18; 詳細
• 細胞内の位置: Host nucleus: P06789
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 298216.59

構造登録者

Abbate, E.A.,Berger, J.M.,Botchan, M.R. (登録日: 2004-06-24, 公開日: 2004-08-24, 最終更新日: 2024-02-14)

主引用文献

Abbate, E.A.,Berger, J.M.,Botchan, M.R.
The X-ray structure of the papillomavirus helicase in complex with its molecular matchmaker E2
Genes Dev., 18:1981-1996, 2004

PubMed Abstract: DNA replication of the papillomaviruses is specified by cooperative binding of two proteins to the ori site: the enhancer E2 and the viral initiator E1, a distant member of the AAA+ family of proteins. Formation of this prereplication complex is an essential step toward the construction of a functional, multimeric E1 helicase and DNA melting. To understand how E2 interacts with E1 to regulate this process, we have solved the X-ray structure of a complex containing the HPV18 E2 activation domain bound to the helicase domain of E1. Modeling the monomers of E1 to a hexameric helicase shows that E2 blocks hexamerization of E1 by shielding a region of the E1 oligomerization surface and stabilizing a conformation of E1 that is incompatible with ATP binding. Further biochemical experiments and structural analysis show that ATP is an allosteric effector of the dissociation of E2 from E1. Our data provide the first molecular insights into how a protein can regulate the assembly of an oligomeric AAA+ complex and explain at a structural level why E2, after playing a matchmaker role by guiding E1 to the DNA, must dissociate for subsequent steps of initiation to occur. Building on previously proposed ideas, we discuss how our data advance current models for the conversion of E1 in the prereplication complex to a hexameric helicase assembly.

PubMed: 15289463
DOI: 10.1101/gad.1220104

実験手法

X-RAY DIFFRACTION (2.1 Å)