Structural characterization of gephyrin by AFM and SAXS reveals a mixture of compact and extended states. (8th October 2013)

• Record Type: Journal Article
• Authors: Sander, Bodo; Tria, Giancarlo; Shkumatov, Alexander V.; Kim, Eun‐Young; Grossmann, J. Günter; Tessmer, Ingrid; Svergun, Dmitri I.; Schindelin, Hermann
• Is Part Of: Acta crystallographica. Volume 69:Part 10(2013:Oct.)
• Page Start: 2050
• Page End: 2060
• Publication Date: 2013-10-08
• Subjects: Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S0907444913018714
• Languages: English
• ISSNs: 0907-4449

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Gephyrin is a trimeric protein involved in the final steps of molybdenum‐cofactor (Moco) biosynthesis and in the clustering of inhibitory glycine and GABA_A receptors at postsynaptic specializations. Each protomer consists of stably folded domains (referred to as the G and E domains) located at either terminus and connected by a proteolytically sensitive linker of ∼150 residues. Both terminal domains can oligomerize in their isolated forms; however, in the context of the full‐length protein only the G‐domain trimer is permanently present, whereas E‐domain dimerization is prevented. Atomic force microscopy (AFM) and small‐angle X‐ray scattering (SAXS) reveal a high degree of flexibility in the structure of gephyrin. The results imply an equilibrium between compact and extended conformational states in solution, with a preference for compact states. CD spectroscopy suggests that a partial compaction is achieved by interactions of the linker with the G and E domains. Taken together, the data provide a rationale for the role of the linker in the overall structure and the conformational dynamics of gephyrin.</p> </abstract>