The C1q-tumor necrosis factor 5 (C1QTNF5) protein plays a significant role in retinal pigmented epithelium (RPE) cellular adhesion. The C1QTNF5 gene is co-transcribed with the frizzled-related protein ( MFRP) gene. A Ser-to-Arg mutation at site 163 (S163R) in C1QTNF5 is known to cause late-onset retinal macular degeneration (L-ORMD). Here we also found that C1QTNF5 monomers can multimerize into a bouquet-like octadecamer. We found that a novel intermolecular hydrogen-bond network of S163 that glues adjacent globular heads of C1QTNF5 together was weakened or abolished by the R163 pathogenic mutation. These findings could underlie the structural basis of this protein's adhesive function and relate to the pathogenesis of its S163R mutation. Additionally, the fact that C1QTNF5 immobilized to a resin selectively enriched detergent extracted membrane-bound MFRP, further confirmed their interaction, implying functions other than cellular adhesion for C1QTNF5.
Bibliographical noteFunding Information:
We thank Dr. Leslie T. Webster Jr. and members of Palczewski’s laboratory (Case Western Reserve University) for valuable comments on the manuscript. This research was supported in part by Grants EY008061 and P30EY11373 from the National Institutes of Health . The work also is based upon research conducted at the Advanced Photon Source on the Northeastern Collaborative Access Team beamlines supported by Grants from the National Center for Research Resources ( 5P41RR015301-10 ) and the National Institute of General Medical Sciences ( 8P41GM103403-10 ) from the National Institutes of Health. Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357.
- Age-related macular degeneration
- Cellular adhesion