Glutamic acid-rich proteins of rod photoreceptors are natively unfolded

Renu Batra-Safferling, Karin Abarca-Heidemann, Heinz Gerd Körschen, Christos Tziatzios, Matthias Stoldt, Ivan Budyak, Dieter Willbold, Harald Schwalbe, Judith Klein-Seetharaman, U. Benjamin Kaupp

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

The outer segment of vertebrate photoreceptors is a specialized compartment that hosts all the signaling components required for visual transduction. Specific to rod photoreceptors is an unusual set of three glutamic acid-rich proteins (GARPs) as follows: two soluble forms, GARP1 and GARP2, and the N-terminal cytoplasmic domain (GARP′ part) of the B1 subunit of the cyclic GMP-gated channel. GARPs have been shown to interact with proteins at the rim of the disc membrane. Here we characterized native GARP1 and GARP2 purified from bovine rod photoreceptors. Amino acid sequence analysis of GARPs revealed structural features typical of "natively unfolded" proteins. By using biophysical techniques, including size-exclusion chromatography, dynamic light scattering, NMRspectroscopy, and circular dichroism, we showed that GARPs indeed exhibit a large degree of intrinsic disorder. Analytical ultracentrifugation and chemical cross-linking showed that GARPs exist in a monomer/multimer equilibrium. The results suggested that the function of GARP proteins is linked to their structural disorder. They may provide flexible spacers or linkers tethering the cyclic GMP-gated channel in the plasma membrane to peripherin at the disc rim to produce a stack of rings of these protein complexes along the long axis of the outer segment. GARP proteins could then provide the environment needed for protein interactions in the rim region of discs.

Original languageEnglish (US)
Pages (from-to)1449-1460
Number of pages12
JournalJournal of Biological Chemistry
Volume281
Issue number3
DOIs
StatePublished - Jan 20 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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