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ARTICLE Structural basis of transmembrane coupling of the HIV-1 envelope glycoprotein Alessandro Piai 1,5 , Qingshan Fu 1,5 , Yongfei Cai 2,3,5 , Fadi Ghantous 4 , Tianshu Xiao 2,3 , Md Munan Shaik 2,3 , Hanqin Peng 2 , Sophia Rits-Volloch 2 , Wen Chen 1 , Michael S. Seaman 4 , Bing Chen 2,3 & James J. Chou 1 The prefusion conformation of HIV-1 envelope protein (Env) is recognized by most broadly neutralizing antibodies (bnAbs). Studies showed that alterations of its membrane-related components, including the transmembrane domain (TMD) and cytoplasmic tail (CT), can reshape the antigenic structure of the Env ectodomain. Using nuclear magnetic resonance (NMR) spectroscopy, we determine the structure of an Env segment encompassing the TMD and a large portion of the CT in bicelles. The structure reveals that the CT folds into amphipathic helices that wrap around the C-terminal end of the TMD, thereby forming a support baseplate for the rest of Env. NMR dynamics measurements provide evidences of dynamic coupling across the TMD between the ectodomain and CT. Pseudovirus-based neutralization assays suggest that CT-TMD interaction preferentially affects antigenic structure near the apex of the Env trimer. These results explain why the CT can modulate the Env antigenic properties and may facilitate HIV-1 Env-based vaccine design. https://doi.org/10.1038/s41467-020-16165-0 OPEN 1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA. 2 Division of Molecular Medicine, Boston Childrens Hospital, Boston, MA 02115, USA. 3 Department of Pediatrics, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115, USA. 4 Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. 5 These authors contributed equally: Alessandro Piai, Qingshan Fu, Yongfei Cai. email: [email protected]; [email protected] NATURE COMMUNICATIONS | (2020)11:2317 | https://doi.org/10.1038/s41467-020-16165-0 | www.nature.com/naturecommunications 1 1234567890():,;
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Page 1: M4 junctions 3 to 12 smart motorway · 2016. 5. 16. · afe r oads reliale our nes infor med travellers n xcuti ancy o t artmnt or Transort Volume 6.0 M4 junctions 3 to 12 smart motorway

Safe roads, reliable journeys, informed travellers

An executive agency of the Department for Transport

Volu

me

6.0

M4 junctions 3 to 12 smart motorway

TR010019

Development consent order application

Volume 6 – Environmental statement and related documents (4 of 5)

March 2015

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Page 3: M4 junctions 3 to 12 smart motorway · 2016. 5. 16. · afe r oads reliale our nes infor med travellers n xcuti ancy o t artmnt or Transort Volume 6.0 M4 junctions 3 to 12 smart motorway

HIGHWAYS AGENCY – M4 JUNCTIONS 3 TO 12 SMART MOTORWAY

CONTENTS

MARCH 2015

Volume 6 Contents

The contents of Volume 6, Environmental Statements and Related Documents, are

shown in the table below.

Folder Document Reference

Document Name Comments

Volume 6, Folder 1 of 5

6.1 Environmental statement

Chapter 1: Introduction

Chapter 2: Scheme context

Chapter 3: Design iterations and alternatives

Chapter 4: Scheme description

Chapter 5: EIA methodology

Chapter 6: Air quality

Chapter 7: Heritage

Chapter 8: Landscape

Chapter 9: Ecology and nature conservation

Chapter 10: Geology and soils

Chapter 11: Materials and waste

Chapter 12: Noise and vibration

Chapter 13: Effects on all travellers

Chapter 14: Community and private assets

Chapter 15: Road drainage and water environment

Chapter 16: Combined and cumulative impacts

Chapter 17: Summary

Chapter 18: References, glossary and list of abbreviations

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HIGHWAYS AGENCY – M4 JUNCTIONS 3 TO 12 SMART MOTORWAY

CONTENTS

MARCH 2015

Folder Document Reference

Document Name Comments

Volume 6, Folder 2 of 5

6.2 Environmental statement figures (1 of 2)

Figure 1.1: Proposed order limits with compounds

Figure 2.1: Scheme location plan

Figure 4.1: Scheme plans

Figure 4.2: Side road alignment drawings

Figures 6.0-6.35: Detailed assessment receptor results

Figure 7.1: Heritage assets

Volume 6, Folder 3 of 5

6.2 Environmental statement figures (2 of 2)

Continuation from Volume 6, Folder 2 of 5

Figure 8.1: Local landscape character areas

Figure 8.2: Visual effects drawings

Figure 8.3: Existing views day and night time

Figure 8.4: Existing landscape character darkness and lighting

Figure 9.1: Study area and statutory designated sites

Figure 9.2: Habitats j3-12

Figure 9.3: Protected species

Figure 10.1: Geology and soils receptors

Figure 12.1: Scheme study area showing noise monitoring locations and sensitive receptors

Figure 12.2: Noise mitigation details

Figure 12.3: Changes in road traffic noise levels (do minimum 2037 minus do minimum 2022)

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HIGHWAYS AGENCY – M4 JUNCTIONS 3 TO 12 SMART MOTORWAY

CONTENTS

MARCH 2015

Folder Document Reference

Document Name Comments

Figure 12.4: Changes in road traffic noise levels (do something 2022 minus do minimum 2022)

Figure 12.5: Change in road traffic noise levels (do something 2037 minus do minimum 2022)

Figure 12.6: Change in road traffic noise levels (do something 2037 minus do minimum 2037)

Figure 14.1: Community and private assets

Figure 15.1: Watercourses and source protection zones

Figure 16.1: Cumulative developments location plan

Volume 6, Folder 4 of 5

6.3 Environmental statement appendices (1 of 2)

Appendix 4.1: Construction programme

Appendix 4.2: Outline environmental management plan (EMP)

Appendix 4.2A: Construction Environmental Management Plan

Includes Annexes A-E

Appendix 4.3: Photomontages

Appendix 5.1: Consultation and scoping report responses

Appendix 5.2: Assessment criteria and significance matrix

Appendix 5.3: Construction compound access

Appendix 6.1: Construction dust mitigation measures

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HIGHWAYS AGENCY – M4 JUNCTIONS 3 TO 12 SMART MOTORWAY

CONTENTS

MARCH 2015

Folder Document Reference

Document Name Comments

Appendix 6.2: Consultation responses from environmental health officers and air quality officers

Appendix 6.3: Quadro technical note

Appendix 6.4: Additional local air quality methodology

Appendix 6.5: Local planning policy

Appendix 6.6: Results for all receptors

Appendix 7.1: Cultural heritage gazeteer

Appendix 7.2: Cultural heritage sensitivity, magnitude of impact and significance of effect criteria

Volume 6, Folder 5 of 5

6.3 Environmental statement appendices (2 of 2)

Continuation from Volume 6, Folder 4 of 5

Appendix 8.1: Landscape and visual amenity sensitivity, magnitude of impact and significance of effect criteria

Appendix 8.2: Landscape and visual amenity local regulatory and policy framework

Appendix 8.3: Visual effects schedules

Appendix 8.4: Schedule of existing vegetation to be retained

Appendix 9.1: Nature conservation technical appendix

Includes Annexes 1-6

Appendix 9.2: Confidential appendix (Badgers)

Not included within public copies

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HIGHWAYS AGENCY – M4 JUNCTIONS 3 TO 12 SMART MOTORWAY

CONTENTS

MARCH 2015

Folder Document Reference

Document Name Comments

Appendix 9.3: Assessment of Implications on European Sites (AIES) matrix

Appendix 9.4: Ecology and nature conservation sensitivity, magnitude of impact and significance of effect criteria

Appendix 9.5: Ecology and nature conservation local regulatory and policy framework

Appendix 10.1: Preliminary Sources Study Report (PSSR)

Appendix 11.1: Materials sensitivity, magnitude of impact and significance of effect criteria

Appendix 11.2: Landfill and waste management facilities

Appendix 11.3: Materials and waste local regulatory and policy framework

Appendix 12.1: Existing noise barriers and existing low noise surfacing

Appendix 12.2: Additional noise barriers and additional low noise surfacing

Appendix 12.3: Construction noise data and results

Appendix 12.4: Important areas

Appendix 12.5: Enhanced mitigation strategy

Appendix 13.1: Effects on all travellers sensitivity and magnitude of impact criteria

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HIGHWAYS AGENCY – M4 JUNCTIONS 3 TO 12 SMART MOTORWAY

CONTENTS

MARCH 2015

Folder Document Reference

Document Name Comments

Appendix 14.1: Community and private assets sensitivity and magnitude of impact criteria

Appendix 14.2: Community and private assets local regulatory and policy framework

Appendix 15.1: Road drainage and the water environment local regulatory and policy framework

Appendix 16.1: Cumulative assessment developments

Appendix 16.2: Traffic modelled cumulative developments

6.4 Environmental statement non-technical summary


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