Nerve growth factor in different crystal forms displays structural flexibility and reveals zinc binding sites

Area of Science:

• Structural Biology
• Neuroscience
• Biochemistry

Background:

• Murine beta-nerve growth factor (beta NGF) is crucial for neuronal survival and development.
• Beta NGF functions as a dimer and is a polypeptide of 118 amino acid residues.

Purpose of the Study:

• To determine the crystal structure of the bis-desocta1-8 form of murine beta NGF.
• To investigate structural variations in beta NGF dimers and their implications for receptor binding.

Main Methods:

• X-ray crystallography was employed to determine the structure in two crystal modifications (space groups P2(1)2(1)2(1) and C2).
• The C2 structure was solved using multiple isomorphous replacement, and the P2(1)2(1)2(1) structure by molecular replacement.
• Refinement was performed to resolutions of 2.5 A and 2.8 A, respectively.

Main Results:

• Two distinct crystal forms of beta NGF were analyzed, revealing dimer structures with high similarity in their core regions.
• Variations were observed in three of the four loop regions extending from the monomer core.
• These loop regions, implicated in receptor binding, showed conformational flexibility.

Conclusions:

• The core structure of beta NGF monomers and their dimer arrangements are conserved.
• Conformational variability in loop regions may facilitate binding to diverse receptors with differing affinities.
• Structural malleability of beta NGF is a key factor in its biological interactions.