Structure-guided identification of a laminin binding site on the laminin receptor precursor.
Structure-guided identification of a laminin binding site on the laminin receptor precursor.
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DOI：
10.1016/j.jmb.2010.10.028
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发表时间：
2011-01-07
影响因子：
5.6
通讯作者：
Meruelo D
中科院分区：
文献类型：
--
作者：
Jamieson KV;Hubbard SR;Meruelo D
The 37/67 kDa human laminin receptor (LamR) is a cell surface receptor for laminin, prion protein, and a variety of viruses. Because of its wide range of ligands, LamR plays a role in numerous pathologies. LamR overexpression correlates with a highly invasive cell phenotype and increased metastatic ability, mediated by interactions between LamR and laminin. In addition, the specific targeting of LamR with small-interfering RNAs (siRNAs), blocking antibodies, and Sindbis viral vectors confers anti-tumor effects. We adopted a structure-based approach to map a laminin binding site on human LamR, by comparing the sequences and crystal structures of LamR and A. fulgidus S2p, a non-laminin binding ortholog. Here, we identify a laminin binding site on LamR, comprising residues Phe32, Glu35, and Arg155, which are conserved among mammalian species. Mutation of these residues results in a significant loss of laminin binding. Further, recombinant wild-type LamR is able to act as a soluble decoy to inhibit cellular migration toward laminin. Mutation of this laminin binding site results in loss of migration inhibition, which demonstrates the physiological role of Phe32, Glu35, and Arg155 for laminin binding activity. Mapping of the LamR binding site should contribute to the development of therapeutics that inhibit LamR interactions with laminin, and may aid in the prevention of tumor growth and metastasis.
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DOI：
10.1093/jnci/85.5.398
发表时间：
1993-03-03
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
MARTIGNONE, S;MENARD, S;COLNAGHI, MI
通讯作者：
COLNAGHI, MI
影响因子：
5.4
作者：
Akache, Bassel;Grimm, Dirk;Kay, Mark A.
通讯作者：
Kay, Mark A.
影响因子：
11.4
作者：
Gauczynski, S;Peyrin, JM;Weiss, S
通讯作者：
Weiss, S
影响因子：
2.9
作者：
GRAF, J;OGLE, RC;KLEINMAN, HK
通讯作者：
KLEINMAN, HK
DOI：
10.1083/jcb.96.5.1475
发表时间：
1983-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Malinoff HL;Wicha MS
通讯作者：
Wicha MS