2E26

Crystal structure of two repeat fragment of reelin

Summary for 2E26

• Entry DOI: 10.2210/pdb2e26/pdb
• Descriptor: Reelin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: signaling protein
• Biological source: Mus musculus (house mouse)
• Cellular location: Secreted, extracellular space, extracellular matrix: Q60841
• Total number of polymer chains: 1
• Total formula weight: 83152.68

Authors

Yasui, N.,Nogi, T.,Kitao, T.,Takagi, J. (deposition date: 2006-11-08, release date: 2007-05-22, Last modification date: 2024-11-06)

Primary citation

Yasui, N.,Nogi, T.,Kitao, T.,Nakano, Y.,Hattori, M.,Takagi, J.
Structure of a receptor-binding fragment of reelin and mutational analysis reveal a recognition mechanism similar to endocytic receptors.
Proc.Natl.Acad.Sci.Usa, 104:9988-9993, 2007

PubMed Abstract: Reelin, a large secreted protein implicated in the cortical development of the mammalian brain, is composed of eight tandem concatenations of "reelin repeats" and binds to neuronal receptors belonging to the low-density lipoprotein receptor gene family. We found that both receptor-binding and subsequent Dab1 phosphorylation occur solely in the segment spanning the fifth and sixth reelin repeats (R5-6). Monomeric fragment exhibited a suboptimal level of signaling activity and artificial oligomerization resulted in a 10-fold increase in activity, indicating the critical importance of higher-order multimerization in physiological reelin. A 2.0-A crystal structure from the R5-6 fragment revealed not only a unique domain arrangement wherein two repeats were aligned side by side with the same orientation, but also the unexpected presence of bound Zn ions. Structure-guided alanine mutagenesis of R5-6 revealed that two Lys residues (Lys-2360 and Lys-2467) constitute a central binding site for the low-density lipoprotein receptor class A module in the receptor, indicating a strong similarity to the ligand recognition mode shared among the endocytic lipoprotein receptors.

PubMed: 17548821
DOI: 10.1073/pnas.0700438104

Experimental method

X-RAY DIFFRACTION (2 Å)