Structural Analysis and Assembly of the HIV-1 Gp41 Amino-Terminal Fusion Peptide and the Pretransmembrane Amphipathic-At-Interface Sequence
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- 作者：Maier Lorizate ; Igor de la Arada ; Nerea Huarte ; Silvia Sá ; nchez-Martí ; nez ; Beatriz G. de la Torre ; David Andreu ; José ; L. R. Arrondo ; José ; L. Nieva
- 刊名：Biochemistry
- 出版年：2006
- 出版时间：December 5, 2006
- 年：2006
- 卷：45
- 期：48
- 页码：14337 - 14346
- 全文大小：449K
- 年卷期：v.45,no.48(December 5, 2006)
- ISSN：1520-4995
文摘
The amino-terminal region within the HIV-1 gp41 aromatic-rich pretransmembrane domainis an amphipathic-at-interface sequence (AIS). AIS is highly conserved between different viral strainsand isolates and recognized by the broadly neutralizing 2F5 antibody. The atomic structure of the nativeFab2F5-bound AIS appears to involve a nonhelical extended region and a 
hars/beta2.gif" BORDER=0 ALIGN="middle">-turn structure. We previouslydescribed how an immunogenic complex forms, based on the stereospecific interactions between AISand the gp41 amino-terminal fusion peptide (FP). Here, we have analyzed the structure generated bythese interactions using synthetic hybrids containing AIS and FP sequences connected through flexibletethers. The monoclonal 2F5 antibody recognized FP-AIS hybrid sequences with an apparently higheraffinity than the linear AIS. Indeed, these hybrids exhibited a weaker capacity to destabilize membranesthan FP alone. A combined structural analysis, including circular dichroism, infrared spectroscopy, andtwo-dimensional infrared correlation spectroscopy, revealed the existence of specific conformations inFP-AIS hybrids, predominantly involving hars/beta2.gif" BORDER=0 ALIGN="middle">-turns. Thermal denaturation studies indicated that FP stabilizesthe nonhelical folded AIS structure. We propose that the assembly of the FP-AIS complex may act asa kinetic trap in halting the capacity of FP to promote fusion.
hars/beta2.gif" BORDER=0 ALIGN="middle">-turn structure. We previouslydescribed how an immunogenic complex forms, based on the stereospecific interactions between AISand the gp41 amino-terminal fusion peptide (FP). Here, we have analyzed the structure generated bythese interactions using synthetic hybrids containing AIS and FP sequences connected through flexibletethers. The monoclonal 2F5 antibody recognized FP-AIS hybrid sequences with an apparently higheraffinity than the linear AIS. Indeed, these hybrids exhibited a weaker capacity to destabilize membranesthan FP alone. A combined structural analysis, including circular dichroism, infrared spectroscopy, andtwo-dimensional infrared correlation spectroscopy, revealed the existence of specific conformations inFP-AIS hybrids, predominantly involving hars/beta2.gif" BORDER=0 ALIGN="middle">-turns. Thermal denaturation studies indicated that FP stabilizesthe nonhelical folded AIS structure. We propose that the assembly of the FP-AIS complex may act asa kinetic trap in halting the capacity of FP to promote fusion.