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PMID- 23708606
OWN - NLM
STAT- MEDLINE
DA - 20130704
DCOM- 20130910
LR - 20150426
IS - 1545-9985 (Electronic)
IS - 1545-9985 (Linking)
VI - 20
IP - 7
DP - 2013 Jul
TI - Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope
glycoprotein gp120.
PG - 796-803
LID - 10.1038/nsmb.2594 [doi]
AB - A substantial proportion of the broadly neutralizing antibodies (bnAbs)
identified in certain HIV-infected donors recognize glycan-dependent epitopes on
HIV-1 gp120. Here we elucidate how the bnAb PGT 135 binds its Asn332
glycan-dependent epitope from its 3.1-A crystal structure with gp120, CD4 and Fab
17b. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR
loops H1 and H3 to penetrate the glycan shield and access the gp120 protein
surface. EM reveals that PGT 135 can accommodate the conformational and chemical
diversity of gp120 glycans by altering its angle of engagement. Combined
structural studies of PGT 135, PGT 128 and 2G12 show that this Asn332-dependent
antigenic region is highly accessible and much more extensive than initially
appreciated, which allows for multiple binding modes and varied angles of
approach; thereby it represents a supersite of vulnerability for antibody
neutralization.
FAU - Kong, Leopold
AU - Kong L
AD - Department of Integrative Structural and Computational Biology, The Scripps
Research Institute, La Jolla, California, USA.
FAU - Lee, Jeong Hyun
AU - Lee JH
FAU - Doores, Katie J
AU - Doores KJ
FAU - Murin, Charles D
AU - Murin CD
FAU - Julien, Jean-Philippe
AU - Julien JP
FAU - McBride, Ryan
AU - McBride R
FAU - Liu, Yan
AU - Liu Y
FAU - Marozsan, Andre
AU - Marozsan A
FAU - Cupo, Albert
AU - Cupo A
FAU - Klasse, Per-Johan
AU - Klasse PJ
FAU - Hoffenberg, Simon
AU - Hoffenberg S
FAU - Caulfield, Michael
AU - Caulfield M
FAU - King, C Richter
AU - King CR
FAU - Hua, Yuanzi
AU - Hua Y
FAU - Le, Khoa M
AU - Le KM
FAU - Khayat, Reza
AU - Khayat R
FAU - Deller, Marc C
AU - Deller MC
FAU - Clayton, Thomas
AU - Clayton T
FAU - Tien, Henry
AU - Tien H
FAU - Feizi, Ten
AU - Feizi T
FAU - Sanders, Rogier W
AU - Sanders RW
FAU - Paulson, James C
AU - Paulson JC
FAU - Moore, John P
AU - Moore JP
FAU - Stanfield, Robyn L
AU - Stanfield RL
FAU - Burton, Dennis R
AU - Burton DR
FAU - Ward, Andrew B
AU - Ward AB
FAU - Wilson, Ian A
AU - Wilson IA
LA - eng
SI - PDB/4JM2
SI - PDB/4JM4
GR - 099197/Wellcome Trust/United Kingdom
GR - P01 AI082362/AI/NIAID NIH HHS/United States
GR - P01 AI82362/AI/NIAID NIH HHS/United States
GR - P30 AI036214/AI/NIAID NIH HHS/United States
GR - P41 GM103310/GM/NIGMS NIH HHS/United States
GR - R01 AI033292/AI/NIAID NIH HHS/United States
GR - R01 AI084817/AI/NIAID NIH HHS/United States
GR - R01 AI33292/AI/NIAID NIH HHS/United States
GR - R01 AI84817/AI/NIAID NIH HHS/United States
GR - R01 GM046192/GM/NIGMS NIH HHS/United States
GR - R37 AI036082/AI/NIAID NIH HHS/United States
GR - R37 AI36082/AI/NIAID NIH HHS/United States
GR - RR017573/RR/NCRR NIH HHS/United States
GR - U01 CA128416/CA/NCI NIH HHS/United States
GR - U54 GM094586/GM/NIGMS NIH HHS/United States
GR - U54 GM094586/GM/NIGMS NIH HHS/United States
GR - UM1 AI100663/AI/NIAID NIH HHS/United States
GR - WT093378MA/Wellcome Trust/United Kingdom
GR - WT099197MA/Wellcome Trust/United Kingdom
GR - Howard Hughes Medical Institute/United States
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
PT - Research Support, U.S. Gov't, Non-P.H.S.
PT - Video-Audio Media
DEP - 20130526
PL - United States
TA - Nat Struct Mol Biol
JT - Nature structural & molecular biology
JID - 101186374
RN - 0 (Alkaloids)
RN - 0 (Antibodies, Neutralizing)
RN - 0 (Antigens, CD4)
RN - 0 (Biopolymers)
RN - 0 (Epitopes)
RN - 0 (HIV Antibodies)
RN - 0 (HIV Envelope Protein gp120)
RN - 0 (Immunoglobulin Fab Fragments)
RN - 0 (Polysaccharides)
RN - 0 (env Gene Products, Human Immunodeficiency Virus)
RN - 0 (gp120 protein, Human immunodeficiency virus 1)
RN - 0 (gp140 envelope protein, Human immunodeficiency virus 1)
RN - 109944-15-2 (kifunensine)
RN - 19130-96-2 (1-Deoxynojirimycin)
RN - ADN3S497AZ (miglustat)
SB - IM
CIN - Nat Struct Mol Biol. 2013 Jul;20(7):771-2. PMID: 23984441
MH - 1-Deoxynojirimycin/analogs & derivatives/pharmacology
MH - Alkaloids/pharmacology
MH - Amino Acid Motifs
MH - Amino Acid Sequence
MH - Antibodies, Neutralizing/chemistry/*immunology/metabolism
MH - Antigen-Antibody Reactions
MH - Antigens, CD4/immunology/metabolism
MH - Binding Sites, Antibody
MH - Biopolymers
MH - Carbohydrate Sequence
MH - Crystallography, X-Ray
MH - Epitopes/chemistry/immunology
MH - Glycosylation/drug effects
MH - HEK293 Cells
MH - HIV Antibodies/chemistry/*immunology/metabolism
MH - HIV Envelope Protein gp120/chemistry/*immunology/metabolism/ultrastructure
MH - Humans
MH - Immunoglobulin Fab Fragments/immunology/metabolism
MH - Microscopy, Electron
MH - Models, Molecular
MH - Molecular Docking Simulation
MH - Molecular Sequence Data
MH - Polysaccharides/physiology
MH - Protein Conformation
MH - Protein Processing, Post-Translational/drug effects
MH - Structure-Activity Relationship
MH - env Gene Products, Human Immunodeficiency Virus/immunology
PMC - PMC3823233
MID - NIHMS464890
OID - NLM: NIHMS464890
OID - NLM: PMC3823233
EDAT- 2013/05/28 06:00
MHDA- 2013/09/11 06:00
CRDT- 2013/05/28 06:00
PHST- 2012/11/02 [received]
PHST- 2013/04/05 [accepted]
PHST- 2013/05/26 [aheadofprint]
AID - nsmb.2594 [pii]
AID - 10.1038/nsmb.2594 [doi]
PST - ppublish
SO - Nat Struct Mol Biol. 2013 Jul;20(7):796-803. doi: 10.1038/nsmb.2594. Epub 2013
May 26. |
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发表于 2016-3-9 21:27:59
发表于 2016-3-10 14:26:33
