PDBsum entry 3d4c

Cell adhesion

PDB id: 3d4c

Contents

Protein chain

470 a.a. *

Ligands

GLC-GLC

Metals

_CD ×7

* Residue conservation analysis

PDB id:

3d4c

Name:

Cell adhesion

Title:

Zp-n domain of mammalian sperm receptor zp3 (crystal form i)

Structure:

Maltose-binding periplasmic protein, linker, zona pellucida protein 3. Chain: a. Fragment: zp3 zp-n domain, unp residues 27-393, unp residues 42-143. Synonym: maltose-binding protein/zp3 zp-n domain chimera, mbp, zona pellucida glycoprotein zp3, sperm receptor, zona pellucida protein c. Engineered: yes. Mutation: yes. Other_details: this protein is a chimera. Residues 2-368 are from e.

Source:

Escherichia coli (strain k12), mus musculus. Organism_taxid: 83333, 10090. Cellular_location: extracellular matrix. Gene: zp3, zp-3, zpc. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.90Å R-factor: 0.192 R-free: 0.227

Authors:

L.Jovine,M.Monne

Key ref:

M.Monné et al. (2008). Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats. Nature, 456, 653-657. PubMed id: 19052627 DOI: 10.1038/nature07599

Date:

14-May-08 Release date: 02-Dec-08

Protein chain

P0AEX9  (MALE_ECOLI) -  Maltose/maltodextrin-binding periplasmic protein from Escherichia coli (strain K12)

Seq: 396 a.a.

Struc: 470 a.a.*

Protein chain

P10761  (ZP3_MOUSE) -  Zona pellucida sperm-binding protein 3 from Mus musculus

Seq: 424 a.a.

Struc: 470 a.a.*

* PDB and UniProt seqs differ at 48 residue positions (black crosses)

DOI no: 10.1038/nature07599

Nature 456:653-657 (2008)

PubMed id: 19052627

Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats.

M.Monné, L.Han, T.Schwend, S.Burendahl, L.Jovine.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2008, 456, 653-657) copyright 2008.

Figures were selected by the author.