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296 a.a.
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144 a.a.
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153 a.a.
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References listed in PDB file
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Key reference
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Title
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Cryo-Em structure of native human uromodulin, A zona pellucida module polymer.
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Authors
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A.Stsiapanava,
C.Xu,
M.Brunati,
S.Zamora-Caballero,
C.Schaeffer,
M.Bokhove,
L.Han,
H.Hebert,
M.Carroni,
S.Yasumasu,
L.Rampoldi,
B.Wu,
L.Jovine.
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Ref.
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EMBO J, 2020,
39,
e106807.
[DOI no: ]
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PubMed id
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Abstract
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Assembly of extracellular filaments and matrices mediating fundamental
biological processes such as morphogenesis, hearing, fertilization, and
antibacterial defense is driven by a ubiquitous polymerization module known as
zona pellucida (ZP) "domain". Despite the conservation of this element
from hydra to humans, no detailed information is available on the filamentous
conformation of any ZP module protein. Here, we report a cryo-electron
microscopy study of uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant
protein in human urine and an archetypal ZP module-containing molecule, in its
mature homopolymeric state. UMOD forms a one-start helix with an unprecedented
180-degree twist between subunits enfolded by interdomain linkers that have
completely reorganized as a result of propeptide dissociation. Lateral
interaction between filaments in the urine generates sheets exposing a
checkerboard of binding sites to capture uropathogenic bacteria, and UMOD-based
models of heteromeric vertebrate egg coat filaments identify a common
sperm-binding region at the interface between subunits.
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Secondary reference #1
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Title
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Characterization and separation of an inhibitor of viral hemagglutination present in urine.
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Authors
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I.Tamm,
F.L.Horsfall.
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Ref.
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Proc Soc Exp Biol Med, 1950,
74,
106-108.
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PubMed id
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Secondary reference #2
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Title
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Etude chimique et ultrastructurale de la glycoprotein tamm et horsfall ou uromucoide.
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Authors
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E.Delain,
J.P.Thiery,
D.Coulard,
A.Joliviene,
L.Hartman.
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Ref.
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biol cellulaire, 1980,
39,
31.
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Secondary reference #3
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Title
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Identification of human uromodulin as the tamm-Horsfall urinary glycoprotein.
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Authors
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D.Pennica,
W.J.Kohr,
W.J.Kuang,
D.Glaister,
B.B.Aggarwal,
E.Y.Chen,
D.V.Goeddel.
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Ref.
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Science, 1987,
236,
83-88.
[DOI no: ]
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PubMed id
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Secondary reference #4
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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 #5
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Title
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Tamm-Horsfall glycoprotein: biology and clinical relevance.
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Authors
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F.Serafini-Cessi,
N.Malagolini,
D.Cavallone.
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Ref.
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Am J Kidney Dis, 2003,
42,
658-676.
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PubMed id
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Secondary reference #6
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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 #7
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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 #8
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Title
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Analysis of uromodulin polymerization provides new insights into the mechanisms regulating zp domain-Mediated protein assembly.
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Authors
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C.Schaeffer,
S.Santambrogio,
S.Perucca,
G.Casari,
L.Rampoldi.
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Ref.
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Mol Biol Cell, 2009,
20,
589-599.
[DOI no: ]
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PubMed id
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Secondary reference #9
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Title
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Insights into egg coat assembly and egg-Sperm interaction from the X-Ray structure of full-Length zp3.
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Authors
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L.Han,
M.Monné,
H.Okumura,
T.Schwend,
A.L.Cherry,
D.Flot,
T.Matsuda,
L.Jovine.
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Ref.
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Cell, 2010,
143,
404-415.
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PubMed id
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Secondary reference #10
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Title
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The rediscovery of uromodulin (tamm-Horsfall protein): from tubulointerstitial nephropathy to chronic kidney disease.
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Authors
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L.Rampoldi,
F.Scolari,
A.Amoroso,
G.Ghiggeri,
O.Devuyst.
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Ref.
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Kidney Int, 2011,
80,
338-347.
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PubMed id
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Secondary reference #11
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Title
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The serine protease hepsin mediates urinary secretion and polymerisation of zona pellucida domain protein uromodulin.
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Authors
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M.Brunati,
S.Perucca,
L.Han,
A.Cattaneo,
F.Consolato,
A.Andolfo,
C.Schaeffer,
E.Olinger,
J.Peng,
S.Santambrogio,
R.Perrier,
S.Li,
M.Bokhove,
A.Bachi,
E.Hummler,
O.Devuyst,
Q.Wu,
L.Jovine,
L.Rampoldi.
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Ref.
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Elife, 2015,
4,
e08887.
[DOI no: ]
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PubMed id
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Secondary reference #12
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Title
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A structured interdomain linker directs self-Polymerization of human uromodulin.
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Authors
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M.Bokhove,
K.Nishimura,
M.Brunati,
L.Han,
D.De sanctis,
L.Rampoldi,
L.Jovine.
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Ref.
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Proc Natl Acad Sci U S A, 2016,
113,
1552-1557.
[DOI no: ]
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PubMed id
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Secondary reference #13
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Title
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Structure of zona pellucida module proteins.
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Authors
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M.Bokhove,
L.Jovine.
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Ref.
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Curr Top Dev Biol, 2018,
130,
413-442.
[DOI no: ]
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PubMed id
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Secondary reference #14
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Title
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Cryo-Em structure of native human uromodulin, A zona pellucida module polymer.
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Authors
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A.Stsiapanava,
C.Xu,
M.Brunati,
S.Zamora-Caballero,
C.Schl.Han,
M.Carroni,
S.Yasumasu,
L.Rampoldi,
B.Wu,
L.Jovine.
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Ref.
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biorxiv ...
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