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Table S1. Function and structure of DENV proteins
Proteins
Functions and special properties
Capsid
Building block of the protein
Structure domains
 N-terminus (the structural protein with the
shell that encloses vRNA, forms
the nucleocapsid (NC) core.
most variability among the flaviviruses)
 Four helices (α1–α4, at aa positions
V26–K35, K45–A58, A63–W69, and K74–N96,
respectively) connected by short loops
 C-terminus (a signal sequence)
PrM
Chaperone for folding and
 Pr (~80aa): seven antiparallel β-strands
assembly of the E protein
(stabilized by three disulphide bonds), two
helices, and two transmembrane helices
 furin cleavage site: Arg-X*-(Lys/Arg)
-Arg
 M peptide (75 aa)
Envelope
Attachment and membrane
 EDIII (aa: 1–100): contains BC, DE and
fusion. An E monomer
FG loops and forms an Ig-like β-barrel
consisting of three -barrel
structure
domains (EDI–III) with folds
 EDII (aa: 109–250): a finger-like
based largely on β-sheets. The
elongated structure with a hydrophobic
EDIII is the receptor-binding
sequence in a loop at its tip
domain. The EDII is a
 EDI (aa: 270–439): located at the
hydrophobic fusion peptide,
N-terminal but with a structurally central
which is sequence conserved
domain connecting EDII and EDIII
among all flaviviruses.
NS1
An unusual viral glycoprotein
 two N-linked glycosylation sites
not found in infectious virion. It  12 hemicystines, and a signalase-like
appears in infected cells
processing site at N-terminus
involved in viral RNA
replication and serves as a serum
marker of disease severity.
NS2A
NS2B
Forms part of the RNA
Contain no conserved motifs characteristic
replication complex
of known enzymes.
Co-factor for NS3 protease.
Residues 67-80 interact with the NS3pro,
flanking hydrophobic regions.
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Table S1. Function and structure of DENV proteins (cont’d)
Proteins
Functions and special properties
NS3
Highly conserved
Structure domains
 NS3pro (~180 aa): consists of six β-strands
multifunctional protein essential
arranged into two β-barrels. The catalytic
for proteolytic activity in
center (His51, Asp75 and Ser135) is located
N-terminus (serine
between these two β-barrels.
apoprotease, NS3 ) and for
pro
 NS3hel (aa: 181–618): subdomain I
RNA replication in C terminus
includes motifs A, B and Ia; subdomain II
hel
(RNA ).
includes motifs III-VI; subdomain III
consists of four α-helices surrounded by
three shorter α-helices and two antiparallel
β-strands..
NS4A
May induce membrane
Contains no conserved motifs characteristic
alterations needed for virus
of known enzymes.
replication.
A small hydrophobic protein (150 aa,
possibly a membrane spanning protein)
with a cytoplasmic N-terminal region and
rich in α-helices followed by two
transmembrane domains separated by a
short peptide and a short C-terminal
domain.
NS4B
May block IFN α/β-induced
A small (248 aa) hydrophobic protein
signal transduction.
containing no conserved motifs
characteristic of known enzymes.
NS5
Methyltransferase (MTase)
 MTase (aa: 1–269): An α/β/β sandwich
responsible for capping and
flanked by N-terminus and C-terminus.
methylating the capped +
 RdRp (aa: 270–900): Composed of six
ssRNA Genome on its 5’
signature-sequence motifs (A-F) and a
terminus and RNA-dependent
priming loop. Organized from the N
RNA (RdRp).
terminus to the C terminus as two nuclear
localization sequences (NLS, aa:
316–368 andNLS, aa: 370–405),
finger (comprises codons 273–315,
416–496, and 543–600), palm (aa:
556–639), and thumb (640–798)
subdomains.
*. X: any amino acid
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