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Published online: 23 July 2008 | doi:10.1038/nchina.2008.169

Structural biology: Two to two

Jane Qiu

Introduction

© (2008) Nature

Neurotrophins — a family of regulators important for the development and function of the central nervous system — control the activity of neurons by interacting with two classes of cell-surface receptors: p75 neurotrophin receptors (p75^NTR), which bind to all neurotrophins; and Trk receptors, which are specific for each neurotrophin. By successfully crystallizing the structure of neurotrophin-3 (NT-3) complexed to p75^NTR, Tao Jiang and co-workers at the Chinese Academy of Sciences in Beijing¹ have shed fresh light on the structural basis for the interaction between neurotrophins and these receptors.

The crystal, which has a structure with a 2.6-Å lattice constant (pictured), contains two NT-3 molecules complexed to one another, around which two p75^NTR receptors bind symmetrically. The result is surprising as a previous study² found an asymmetrical complex, in which two molecules of nerve growth factor (NGF) — another type of neurotrophin — were crystallized to a single p75^NTR receptor.

Jiang and co-workers found that both NT-3 and NGF bind to p75^NTR at a two-to-two ratio in solution, which is consistent with the symmetrical model of interaction. When the deglycosylated (without any sugar groups) form of p75^NTR was used, however, two neurotrophin molecules could bind to one p75^NTR only.

Because the symmetrical complex contains glycosylated p75^NTR, it represents a native state of receptor activation, whereas the previously reported structure was a result of artificial deglycosylation. The findings have important implications for our understanding of neurotrophin action, and might enable the development of new therapeutic strategies for modulating their functions.

The authors of this work are from:
National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

References

1. Gong, Y., Cao, P., Yu, H. J. & Jiang, T. Crystal structure of the neurotrophin-3 and p75^NTR symmetrical complex. Nature doi: 10.1038/nature07089 (2008). | Article |
2. He, X. L. & Garcia, K. C. Structure of nerve growth factor complexed with the shared neurotrophin receptor p75. Science 304, 870–875 (2004). | Article | PubMed | ISI | ChemPort |