Structural highlights
Function[NGF_MOUSE] Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades through those receptor tyrosine kinase to regulate neuronal proliferation, differentiation and survival. Publication Abstract from PubMedNerve Growth Factor (NGF), the prototype of the neurotrophin family, is essential for maintenance and growth of different neuronal populations. The X-ray crystal structure of NGF has been known since the early '90s and shows a beta-sandwich fold with extensive loops that are involved in the interaction with its binding partners. Understanding the dynamical properties of these loops is thus important for molecular recognition. We present here a combined solution NMR/molecular dynamics study which addresses the question of whether and how much the long loops of NGF are flexible and describes the N-terminal intrinsic conformational tendency of the unbound NGF molecule. NMR titration experiments allowed identification of a previously undetected epitope of the anti-NGF antagonist antibody alphaD11 which will be of crucial importance for future drug lead discovery. The present study thus recapitulates all the available structural information and unveils the conformational versatility of the relatively rigid NGF loops upon functional ligand binding. Conformational Rigidity within Plasticity Promotes Differential Target Recognition of Nerve Growth Factor.,Paoletti F, de Chiara C, Kelly G, Covaceuszach S, Malerba F, Yan R, Lamba D, Cattaneo A, Pastore A Front Mol Biosci. 2016 Dec 26;3:83. doi: 10.3389/fmolb.2016.00083. eCollection, 2016. PMID:28083536[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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