3V65

Crystal structure of agrin and LRP4 complex

Summary for 3V65

• Entry DOI: 10.2210/pdb3v65/pdb
• Related: 3V64
• Descriptor: Agrin, Low-density lipoprotein receptor-related protein 4, CALCIUM ION (3 entities in total)
• Functional Keywords: laminin-g, beta-propeller, protein binding
• Biological source: Rattus norvegicus (rat); More
• Cellular location: Secreted, extracellular space, extracellular matrix: P25304; Membrane; Single-pass type I membrane protein (Potential): Q9QYP1
• Total number of polymer chains: 4
• Total formula weight: 128765.02

Authors

Zong, Y.,Jin, R. (deposition date: 2011-12-18, release date: 2012-04-25, Last modification date: 2024-10-30)

Primary citation

Zong, Y.,Zhang, B.,Gu, S.,Lee, K.,Zhou, J.,Yao, G.,Figueiredo, D.,Perry, K.,Mei, L.,Jin, R.
Structural basis of agrin-LRP4-MuSK signaling.
Genes Dev., 26:247-258, 2012

PubMed Abstract: Synapses are the fundamental units of neural circuits that enable complex behaviors. The neuromuscular junction (NMJ), a synapse formed between a motoneuron and a muscle fiber, has contributed greatly to understanding of the general principles of synaptogenesis as well as of neuromuscular disorders. NMJ formation requires neural agrin, a motoneuron-derived protein, which interacts with LRP4 (low-density lipoprotein receptor-related protein 4) to activate the receptor tyrosine kinase MuSK (muscle-specific kinase). However, little is known of how signals are transduced from agrin to MuSK. Here, we present the first crystal structure of an agrin-LRP4 complex, consisting of two agrin-LRP4 heterodimers. Formation of the initial binary complex requires the z8 loop that is specifically present in neuronal, but not muscle, agrin and that promotes the synergistic formation of the tetramer through two additional interfaces. We show that the tetrameric complex is essential for neuronal agrin-induced acetylcholine receptor (AChR) clustering. Collectively, these results provide new insight into the agrin-LRP4-MuSK signaling cascade and NMJ formation and represent a novel mechanism for activation of receptor tyrosine kinases.

PubMed: 22302937
DOI: 10.1101/gad.180885.111

Experimental method

X-RAY DIFFRACTION (3.3 Å)