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PDBsum entry 4m17
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Sugar binding protein
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PDB id
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4m17
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PDB id:
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| Name: |
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Sugar binding protein
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Title:
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Crystal structure of surfactant protein-d d325a/r343v mutant
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Structure:
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Pulmonary surfactant-associated protein d. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Fragment: neck and carbohydrate recognition domain (unp residues 229- 375). Synonym: psp-d, sp-d, collectin-7, lung surfactant protein d. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: colec7, pspd, sftp4, sftpd. Expressed in: escherichia coli. Expression_system_taxid: 511693.
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Resolution:
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2.10Å
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R-factor:
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0.170
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R-free:
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0.188
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Authors:
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B.C.Goh,M.J.Rynkiewicz,T.R.Cafarella,M.R.White,K.L.Hartshorn,K.Allen, E.C.Crouch,O.Calin,P.H.Seeberger,K.Schulten,B.A.Seaton
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Key ref:
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B.C.Goh
et al.
(2013).
Molecular mechanisms of inhibition of influenza by surfactant protein D revealed by large-scale molecular dynamics simulation.
Biochemistry,
52,
8527-8538.
PubMed id:
DOI:
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Date:
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02-Aug-13
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Release date:
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04-Dec-13
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PROCHECK
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Headers
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References
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P35247
(SFTPD_HUMAN) -
Pulmonary surfactant-associated protein D from Homo sapiens
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Seq:
Struc:
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375 a.a.
140 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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DOI no:
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Biochemistry
52:8527-8538
(2013)
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PubMed id:
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Molecular mechanisms of inhibition of influenza by surfactant protein D revealed by large-scale molecular dynamics simulation.
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B.C.Goh,
M.J.Rynkiewicz,
T.R.Cafarella,
M.R.White,
K.L.Hartshorn,
K.Allen,
E.C.Crouch,
O.Calin,
P.H.Seeberger,
K.Schulten,
B.A.Seaton.
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ABSTRACT
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Surfactant protein D (SP-D), a mammalian C-type lectin, is the primary innate
inhibitor of influenza A virus (IAV) in the lung. Interactions of SP-D with
highly branched viral N-linked glycans on hemagglutinin (HA), an abundant IAV
envelope protein and critical virulence factor, promote viral aggregation and
neutralization through as yet unknown molecular mechanisms. Two truncated human
SP-D forms, wild-type (WT) and double mutant D325A+R343V, representing neck and
carbohydrate recognition domains are compared in this study. Whereas both WT and
D325A+R343V bind to isolated glycosylated HA, WT does not inhibit IAV in
neutralization assays; in contrast, D325A+R343V neutralization compares well
with that of full-length native SP-D. To elucidate the mechanism for these
biochemical observations, we have determined crystal structures of D325A+R343V
in the presence and absence of a viral nonamannoside (Man9). On the basis of the
D325A+R343V-Man9 structure and other crystallographic data, models of complexes
between HA and WT or D325A+R343V were produced and subjected to molecular
dynamics. Simulations reveal that whereas WT and D325A+R343V both block the
sialic acid receptor site of HA, the D325A+R343V complex is more stable, with
stronger binding caused by additional hydrogen bonds and hydrophobic
interactions with HA residues. Furthermore, the blocking mechanism of HA differs
for WT and D325A+R343V because of alternate glycan binding modes. The combined
results suggest a mechanism through which the mode of SP-D-HA interaction could
significantly influence viral aggregation and neutralization. These studies
provide the first atomic-level molecular view of an innate host defense lectin
inhibiting its viral glycoprotein target.
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Links
