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PDBsum entry 3d4c
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Cell adhesion
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PDB id
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3d4c
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the zp-N domain of zp3 reveals the core fold of animal egg coats.
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Authors
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M.Monné,
L.Han,
T.Schwend,
S.Burendahl,
L.Jovine.
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Ref.
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Nature, 2008,
456,
653-657.
[DOI no: ]
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PubMed id
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Abstract
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Species-specific recognition between the egg extracellular matrix (zona
pellucida) and sperm is the first, crucial step of mammalian fertilization. Zona
pellucida filament components ZP3 and ZP2 act as sperm receptors, and mice
lacking either of the corresponding genes produce oocytes without a zona
pellucida and are completely infertile. Like their counterparts in the vitelline
envelope of non-mammalian eggs and many other secreted eukaryotic proteins, zona
pellucida subunits polymerize using a 'zona pellucida (ZP) domain' module, whose
conserved amino-terminal part (ZP-N) was suggested to constitute a domain of its
own. No atomic structure has been reported for ZP domain proteins, and there is
no structural information on any conserved vertebrate protein that is essential
for fertilization and directly involved in egg-sperm binding. Here we describe
the 2.3 ångström (A) resolution structure of the ZP-N fragment of mouse
primary sperm receptor ZP3. The ZP-N fold defines a new immunoglobulin
superfamily subtype with a beta-sheet extension characterized by an E' strand
and an invariant tyrosine residue implicated in polymerization. The structure
strongly supports the presence of ZP-N repeats within the N-terminal region of
ZP2 and other vertebrate zona pellucida/vitelline envelope proteins, with
implications for overall egg coat architecture, the post-fertilization block to
polyspermy and speciation. Moreover, it provides an important framework for
understanding human diseases caused by mutations in ZP domain proteins and
developing new methods of non-hormonal contraception.
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Figure 1.
Figure 1: Overall structure of the ZP-N domain of ZP3. a,
Cartoon representation rainbow-coloured from blue (N terminus)
to red (C terminus), with conserved disulphides shown as grey
sticks. b, Topology, with strands as triangles, and helices as
circles. Connections between secondary structure elements at the
top, middle or bottom of the structure are represented by
straight continuous, rounded dashed and straight dashed lines,
respectively. c, Structure-based alignment of ZP-N sequences of
mouse (m) and human (h) zona pellucida proteins, as well as
non-egg coat ZP domain proteins  -tectorin
(TECTA), endoglin (ENG) and uromodulin (UMOD). Consensus
sequences (cons.) for ZP3 homologues and Pfam ZP domain family
seed sequences are also shown (for colour-coding and consensus
keys, see Methods). Brown circles mark residues in which the
side chains lie on the inner side of  -sheets;
open and closed black boxes indicate conserved hydrophobic core
and Cys residues, respectively.
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Figure 4.
Figure 4: Model of the ZP-N domain repeat region of ZP2. a,
b, Domain architecture of ZP2 (a) and three-dimensional surface
model of its ZP-N1–N4 region (b), with relevant features
indicated (see Supplementary Table 5). aa, amino acids.
Glycosylation and positively selected sites are dark blue and
violet, respectively. Unless otherwise specified, the residue
numbers refer to mouse ZP2 sequence. mAb, monoclonal antibody.
c, Detail of the region boxed in b, highlighting a further
disulphide bond between non-canonical Cys residues of ZP-N3. d,
View of the region circled in b, suggesting that
post-fertilization cleavage of ZP-N2 BC loop could affect the
position of ZP-N1 relative to the rest of ZP2.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2008,
456,
653-657)
copyright 2008.
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Secondary reference #1
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Title
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Mammalian sperm-Egg interaction: identification of a glycoprotein in mouse egg zonae pellucidae possessing receptor activity for sperm.
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Authors
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J.D.Bleil,
P.M.Wassarman.
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Ref.
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Cell, 1980,
20,
873-882.
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PubMed id
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Secondary reference #2
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Title
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A large domain common to sperm receptors (zp2 and zp3) and tgf-Beta type III receptor.
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Authors
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P.Bork,
C.Sander.
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Ref.
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Febs Lett, 1992,
300,
237-240.
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PubMed id
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Secondary reference #3
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Title
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The zp domain is a conserved module for polymerization of extracellular proteins.
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Authors
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L.Jovine,
H.Qi,
Z.Williams,
E.Litscher,
P.M.Wassarman.
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Ref.
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Nat Cell Biol, 2002,
4,
457-461.
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PubMed id
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Secondary reference #4
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Title
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A duplicated motif controls assembly of zona pellucida domain proteins.
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Authors
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L.Jovine,
H.Qi,
Z.Williams,
E.S.Litscher,
P.M.Wassarman.
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Ref.
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Proc Natl Acad Sci U S A, 2004,
101,
5922-5927.
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PubMed id
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Secondary reference #5
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Title
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Zona pellucida domain proteins.
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Authors
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L.Jovine,
C.C.Darie,
E.S.Litscher,
P.M.Wassarman.
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Ref.
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Annu Rev Biochem, 2005,
74,
83.
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PubMed id
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Secondary reference #6
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Title
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The plac1-Homology region of the zp domain is sufficient for protein polymerisation.
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Authors
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L.Jovine,
W.G.Janssen,
E.S.Litscher,
P.M.Wassarman.
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Ref.
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Bmc Biochem, 2006,
7,
11.
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PubMed id
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