Reference 4



J Cell Sci Suppl 13: 19-30 (1990)[91193283] 

X-ray crystallographic studies on murine nerve growth
factor.

N. Q. McDonald, R. Lapatto, J. Murray-Rust & T. L. Blundell

Laboratory of Molecular Biology, Birkbeck College, London, UK. 

The largest and best characterised family of neurotrophic growth factors is that of
nerve growth factor (NGF) and its relatives. In order to understand the relation of
structure and function, we have undertaken X-ray analyses of murine NGF. The active
component beta-NGF crystallises as hexagonal bipyramids that give good X-ray
diffraction data using a synchrotron to 2.3A resolution. We have prepared several heavy
atom derivatives that are being used in the method of multiple isomorphous replacement
to solve the phase problem and determine the three-dimensional structure. We have also
prepared crystals of the precursor, 7S NGF, which is a complex of three different
subunits of composition alpha 2 beta 2 gamma 2. We have collected X-ray data to 3A
resolution on two crystal forms with related cell dimensions and orthorhombic
spacegroups. Detailed analyses of the structures of NGF in these crystal forms, taken
together with data on sequence and biological activity, should give clues concerning the
role of the precursor complex in storage and assist the identification of the surface
region involved in receptor binding.

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