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- PDB-5bup: Crystal structure of the ZP-C domain of mouse ZP2 -

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Entry
Database: PDB / ID: 5bup
TitleCrystal structure of the ZP-C domain of mouse ZP2
ComponentsZona pellucida sperm-binding protein 2
KeywordsCELL ADHESION / Sperm receptor / immunoglobulin-like domain / zona pellucida / ZP domain / protein polymerization
Function / homology
Function and homology information


Interaction With Cumulus Cells And The Zona Pellucida / structural constituent of egg coat / egg coat / acrosin binding / prevention of polyspermy / binding of sperm to zona pellucida / multivesicular body / collagen-containing extracellular matrix / endoplasmic reticulum / extracellular region ...Interaction With Cumulus Cells And The Zona Pellucida / structural constituent of egg coat / egg coat / acrosin binding / prevention of polyspermy / binding of sperm to zona pellucida / multivesicular body / collagen-containing extracellular matrix / endoplasmic reticulum / extracellular region / identical protein binding / plasma membrane
Similarity search - Function
Zona pellucida, ZP-C domain / : / : / Zona pellucida domain, conserved site / ZP domain signature. / Zona pellucida, ZP-C domain / Zona pellucida-like domain / Zona pellucida (ZP) domain / ZP domain profile. / Zona pellucida domain ...Zona pellucida, ZP-C domain / : / : / Zona pellucida domain, conserved site / ZP domain signature. / Zona pellucida, ZP-C domain / Zona pellucida-like domain / Zona pellucida (ZP) domain / ZP domain profile. / Zona pellucida domain / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
ACETATE ION / Zona pellucida sperm-binding protein 2
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.251 Å
AuthorsNishimura, K. / Jovine, L.
Funding support Sweden, 7items
OrganizationGrant numberCountry
Karolinska Institutet Sweden
Center for Biosciences Sweden
Swedish Research Council2012-5093 Sweden
Goran Gustafsson Foundation for Research in Natural Sciences and Medicine Sweden
Sven and Ebba-Christina Hagberg foundation Sweden
European Molecular Biology Organization
European UnionERC 260759
Citation
Journal: Proc Natl Acad Sci U S A / Year: 2016
Title: A structured interdomain linker directs self-polymerization of human uromodulin.
Authors: Marcel Bokhove / Kaoru Nishimura / Martina Brunati / Ling Han / Daniele de Sanctis / Luca Rampoldi / Luca Jovine /
Abstract: Uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant human urinary protein, plays a key role in chronic kidney diseases and is a promising therapeutic target for hypertension. Via its bipartite ...Uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant human urinary protein, plays a key role in chronic kidney diseases and is a promising therapeutic target for hypertension. Via its bipartite zona pellucida module (ZP-N/ZP-C), UMOD forms extracellular filaments that regulate kidney electrolyte balance and innate immunity, as well as protect against renal stones. Moreover, salt-dependent aggregation of UMOD filaments in the urine generates a soluble molecular net that captures uropathogenic bacteria and facilitates their clearance. Despite the functional importance of its homopolymers, no structural information is available on UMOD and how it self-assembles into filaments. Here, we report the crystal structures of polymerization regions of human UMOD and mouse ZP2, an essential sperm receptor protein that is structurally related to UMOD but forms heteropolymers. The structure of UMOD reveals that an extensive hydrophobic interface mediates ZP-N domain homodimerization. This arrangement is required for filament formation and is directed by an ordered ZP-N/ZP-C linker that is not observed in ZP2 but is conserved in the sequence of deafness/Crohn's disease-associated homopolymeric glycoproteins α-tectorin (TECTA) and glycoprotein 2 (GP2). Our data provide an example of how interdomain linker plasticity can modulate the function of structurally similar multidomain proteins. Moreover, the architecture of UMOD rationalizes numerous pathogenic mutations in both UMOD and TECTA genes.
#1: Journal: Proc. Natl. Acad. Sci. U.S.A. / Year: 1980
Title: Synthesis of zona pellucida proteins by denuded and follicle-enclosed mouse oocytes during culture in vitro.
Authors: Bleil, J.D. / Wassarman, P.M.
#2: Journal: Dev. Biol. / Year: 1981
Title: Mammalian sperm-egg interaction: fertilization of mouse eggs triggers modification of the major zona pellucida glycoprotein, ZP2.
Authors: Bleil, J.D. / Beall, C.F. / Wassarman, P.M.
#3: Journal: J. Biol. Chem. / Year: 2003
Title: Structural characterization of native mouse zona pellucida proteins using mass spectrometry.
Authors: Boja, E.S. / Hoodbhoy, T. / Fales, H.M. / Dean, J.
#4: Journal: Mol. Reprod. Dev. / Year: 2008
Title: Disulfide linkage patterns of pig zona pellucida glycoproteins ZP3 and ZP4.
Authors: Kanai, S. / Kitayama, T. / Yonezawa, N. / Sawano, Y. / Tanokura, M. / Nakano, M.
#5: Journal: Cell / Year: 2010
Title: Insights into egg coat assembly and egg-sperm interaction from the X-ray structure of full-length ZP3.
Authors: Ling Han / Magnus Monné / Hiroki Okumura / Thomas Schwend / Amy L Cherry / David Flot / Tsukasa Matsuda / Luca Jovine /
Abstract: ZP3, a major component of the zona pellucida (ZP) matrix coating mammalian eggs, is essential for fertilization by acting as sperm receptor. By retaining a propeptide that contains a polymerization- ...ZP3, a major component of the zona pellucida (ZP) matrix coating mammalian eggs, is essential for fertilization by acting as sperm receptor. By retaining a propeptide that contains a polymerization-blocking external hydrophobic patch (EHP), we determined the crystal structure of an avian homolog of ZP3 at 2.0 Å resolution. The structure unveils the fold of a complete ZP domain module in a homodimeric arrangement required for secretion and reveals how EHP prevents premature incorporation of ZP3 into the ZP. This suggests mechanisms underlying polymerization and how local structural differences, reflected by alternative disulfide patterns, control the specificity of ZP subunit interaction. Close relative positioning of a conserved O-glycan important for sperm binding and the hypervariable, positively selected C-terminal region of ZP3 suggests a concerted role in the regulation of species-restricted gamete recognition. Alternative conformations of the area around the O-glycan indicate how sperm binding could trigger downstream events via intramolecular signaling.
History
DepositionJun 4, 2015Deposition site: RCSB / Processing site: PDBE
Revision 1.0Jan 27, 2016Provider: repository / Type: Initial release
Revision 1.1Feb 10, 2016Group: Database references
Revision 1.2Feb 17, 2016Group: Database references
Revision 1.3Sep 6, 2017Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Oct 23, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Zona pellucida sperm-binding protein 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)24,0044
Polymers23,8271
Non-polymers1773
Water1,27971
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area640 Å2
ΔGint-2 kcal/mol
Surface area9030 Å2
MethodPISA
Unit cell
Length a, b, c (Å)105.210, 105.210, 40.550
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number169
Space group name H-MP61

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Components

#1: Protein Zona pellucida sperm-binding protein 2 / Zona pellucida glycoprotein 2 / Zp-2 / Zona pellucida protein A


Mass: 23826.770 Da / Num. of mol.: 1 / Fragment: UNP residues 463-664 / Mutation: K634N, R635A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Zp2, Zp-2, Zpa / Plasmid: pHLsec / Cell line (production host): HEK-293T / Production host: Homo sapiens (human) / References: UniProt: P20239
#2: Chemical ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H3O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 71 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION

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Sample preparation

CrystalDensity Matthews: 2.7 Å3/Da / Density % sol: 54.5 % / Description: Needle
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.5
Details: 25% PEG 3350, 0.1 M sodium acetate pH 5.5, 0.2 M ammonium sulfate, 20% glycerol

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.97939 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 29, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97939 Å / Relative weight: 1
ReflectionResolution: 2.25057→45.5573 Å / Num. obs: 12293 / % possible obs: 95 % / Redundancy: 3.4 % / Rmerge(I) obs: 0.1022 / Net I/σ(I): 9.74
Reflection shellResolution: 2.251→2.332 Å / Redundancy: 3.3 % / Mean I/σ(I) obs: 1.19 / % possible all: 100

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Processing

Software
NameVersionClassification
XDS20141103data reduction
PHASER2.5.7phasing
Coot0.8.1model building
PHENIXdev-1924refinement
XDSdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.251→37.05 Å / SU ML: 0.33 / Cross valid method: FREE R-VALUE / σ(F): 0 / Phase error: 26.02 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2283 1174 9.94 %RANDOM
Rwork0.2014 ---
obs0.2042 11813 95.48 %-
Solvent computationShrinkage radii: 0.6 Å / VDW probe radii: 0.9 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.251→37.05 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1266 0 12 71 1349
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0051309
X-RAY DIFFRACTIONf_angle_d0.8591782
X-RAY DIFFRACTIONf_dihedral_angle_d13.472481
X-RAY DIFFRACTIONf_chiral_restr0.03198
X-RAY DIFFRACTIONf_plane_restr0.004230
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.2506-2.36920.36251490.3431387X-RAY DIFFRACTION89
2.3692-2.51770.34841660.30361469X-RAY DIFFRACTION93
2.5177-2.7120.29831580.27561473X-RAY DIFFRACTION93
2.712-2.98490.24621700.22791514X-RAY DIFFRACTION96
2.9849-3.41670.19921720.17711574X-RAY DIFFRACTION98
3.4167-4.30420.18731710.14761588X-RAY DIFFRACTION99
4.3042-45.56660.20451880.181634X-RAY DIFFRACTION99
Refinement TLS params.

Details: Chain A / Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
13.7121-0.5888-0.32212.25630.20143.6076-0.04390.2680.0267-0.0056-0.01030.2557-0.0079-0.26080.00020.26850.0543-0.01590.3190.02020.266916.570550.070112.3442
20.1830.046-0.14810.40020.29740.39710.2738-0.250.07880.544-0.42890.3127-0.1877-0.1614-0.0020.53510.01920.04020.7182-0.08320.61134.769656.101925.6329
30.89640.41050.21490.71330.36820.21170.06770.51570.353-0.28540.1295-0.0996-0.0442-0.2918-0.01570.25070.10630.02170.37540.05260.279224.077652.488711.4111
Refinement TLS group
IDRefine-IDRefine TLS-IDSelectionSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allchain A and resi 642:656A642 - 656
2X-RAY DIFFRACTION2chain A and resi 614:641
3X-RAY DIFFRACTION3chain A and resi 642:656

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