TY - JOUR
T1 - Structural Basis for Specific Recognition of Reelin by Its Receptors
AU - Yasui, Norihisa
AU - Nogi, Terukazu
AU - Takagi, Junichi
N1 - Funding Information:
We would like to thank Y. Yamada, N. Matsugaki, and N. Igarashi of Photon Factory and E. Yamashita, M. Yoshimura, M. Suzuki, and A. Nakagawa of SPring-8 BL-44XU for their help with X-ray data collection; K. Tamura-Kawakami, E. Mihara, and M. Nampo for their excellent technical support; S. Tabata for preparation of LA module proteins; and M. Nakano for preparation of the manuscript. This work was partly supported by the Grant-in-Aid for Scientific Research (A) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), by the Grant-in-Aid for Scientific Research on Priority Areas from MEXT, and by the Protein 3000 Project grant from MEXT. The authors declare that they have no competing financial interests.
PY - 2010/3/10
Y1 - 2010/3/10
N2 - Apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor, members of the low-density lipoprotein receptor (LDLR) protein family, function as neuronal receptors for a secreted glycoprotein reelin during brain development. In both receptors, the first LDLR class A (LA1) module is sufficient to bind reelin. Analysis of a 2.6 Å crystal structure of the reelin receptor-binding fragment in complex with the LA1 of ApoER2 revealed that Lys2467 of reelin is recognized by both a conserved Trp residue and calcium-coordinating acidic residues from LA1, which together with Lys2360 plays a critical role in the interaction. This "double-Lys" recognition mode is, in fact, shared among other LDLR family proteins in ligand binding. The interface between reelin and LA1 covers a small surface area of ∼350 Å2 on each side, which ensures a stable complex formation under physiological conditions. An examination of structure-guided mutagenesis on interface residues revealed key features of this interaction.
AB - Apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor, members of the low-density lipoprotein receptor (LDLR) protein family, function as neuronal receptors for a secreted glycoprotein reelin during brain development. In both receptors, the first LDLR class A (LA1) module is sufficient to bind reelin. Analysis of a 2.6 Å crystal structure of the reelin receptor-binding fragment in complex with the LA1 of ApoER2 revealed that Lys2467 of reelin is recognized by both a conserved Trp residue and calcium-coordinating acidic residues from LA1, which together with Lys2360 plays a critical role in the interaction. This "double-Lys" recognition mode is, in fact, shared among other LDLR family proteins in ligand binding. The interface between reelin and LA1 covers a small surface area of ∼350 Å2 on each side, which ensures a stable complex formation under physiological conditions. An examination of structure-guided mutagenesis on interface residues revealed key features of this interaction.
KW - CELLBIO
KW - PROTEINS
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U2 - 10.1016/j.str.2010.01.010
DO - 10.1016/j.str.2010.01.010
M3 - Article
C2 - 20223215
AN - SCOPUS:77649144078
SN - 0969-2126
VL - 18
SP - 320
EP - 331
JO - Structure with Folding & design
JF - Structure with Folding & design
IS - 3
ER -