Structural Features of Paramyxovirus F Protein Required for Fusion Initiation

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• 作者：Richard K. Plemper ; Ami S. Lakdawala ; Kim M. Gernert ; James P. Snyder ; and Richard W. Compans
• 刊名：Biochemistry
• 出版年：2003
• 出版时间：June 10, 2003
• 年：2003
• 卷：42
• 期：22
• 页码：6645 - 6655
• 全文大小：1202K
• 年卷期：v.42,no.22(June 10, 2003)
• ISSN：1520-4995

文摘

On the basis of the coordinates of the related Newcastle disease virus (NDV) F protein, Valine-94, a determinant of measles virus (MV) cytopathicity, is predicted to lie in a cylindrical cavity with 10Å diameter located at the F neck. A 16-residue domain around V94 is functionally interchangeable betweenNDV and MV F, supporting our homology model. Features of the cavity are conserved within theParamyxovirinae. A hydrophobic base and a hydrophilic residue at the rim are required for surfaceexpression. Small residue substitutions predicted to open the cavity were found to disrupt transport orlimit fusogenicity of transport-competent mutants but can be compensated for by simultaneous insertionof larger residues at the opposing wall. Variants containing histidine substitutions mediate fusion at pH8.5, while at pH 7.2 fusion is blocked, suggesting that functionality requires low charge in the cavity.These results indicate that specific structural features of the cavity are essential for paramyxovirus fusioninitiation.