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Title
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Structure of the C-terminal laminin G-like domain pair of the laminin alpha2 chain harbouring binding sites for alpha-dystroglycan and heparin.
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Authors
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D.Tisi,
J.F.Talts,
R.Timpl,
E.Hohenester.
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Ref.
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EMBO J, 2000,
19,
1432-1440.
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PubMed id
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Abstract
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The laminins are large heterotrimeric glycoproteins with fundamental roles in
basement membrane architecture and function. The C-terminus of the laminin alpha
chain contains a tandem of five laminin G-like (LG) domains. We report the 2.0 A
crystal structure of the laminin alpha2 LG4-LG5 domain pair, which harbours
binding sites for heparin and the cell surface receptor alpha-dystroglycan, and
is 41% identical to the laminin alpha1 E3 fragment. LG4 and LG5 are arranged in
a V-shaped fashion related by a 110 degrees rotation about an axis passing near
the domain termini. An extended N-terminal segment is disulfide bonded to LG5
and stabilizes the domain pair. Two calcium ions, one each in LG4 and LG5, are
located 65 A apart at the tips of the domains opposite the polypeptide termini.
An extensive basic surface region between the calcium sites is proposed to bind
alpha-dystroglycan and heparin. The LG4-LG5 structure was used to construct a
model of the laminin LG1-LG5 tandem and interpret missense mutations underlying
protein S deficiency.
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