4F3J

Crystal Structure of Trimeric gC1q Domain of Human C1QTNF5 associated with Late-onset Retinal Macular Degeneration

Summary for 4F3J

• Entry DOI: 10.2210/pdb4f3j/pdb
• Descriptor: Complement C1q tumor necrosis factor-related protein 5 (2 entities in total)
• Functional Keywords: late-onset retinal macular degeneration, l-ormd, l-ord, amd, age-related macular degeneration, c1qtnf5, ctrp5, s163r, ser163arg, drusen, retinal deposites, 10-strand jelly-roll fold, mfrp, rpe, ciliary body, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted (Probable): Q9BXJ0
• Total number of polymer chains: 1
• Total formula weight: 16424.30

Authors

Tu, X.,Palczewski, K. (deposition date: 2012-05-09, release date: 2012-11-07, Last modification date: 2024-02-28)

Primary citation

Tu, X.,Palczewski, K.
Crystal structure of the globular domain of C1QTNF5: Implications for late-onset retinal macular degeneration.
J.Struct.Biol., 180:439-446, 2012

PubMed Abstract: Autosomal dominant late-onset retinal macular degeneration (L-ORMD) is caused by a single S163R mutation in the C1q and tumor necrosis factor-related protein 5 (C1QTNF5) gene. The C1QTNF5 gene encodes a secreted and membrane-associated protein involved in adhesion of retinal pigmented epithelial cells (RPE) to Bruch's membrane. The crystal structure of the trimeric globular domain of human C1QTNF5 at 1.34Å resolution reveals unique features of this novel C1q family member. It lacks a Ca²⁺-binding site, displays a remarkable non-uniform distribution of surface electrostatic potentials and possesses a unique sequence (F₁₈₁F₁₈₂G₁₈₃G₁₈₄W₁₈₅P₁₈₆) that forms a hydrophobic plateau surrounded by Lys and Arg residues with a solvent cavity underneath. S₁₆₃ forms a hydrogen bond with F₁₈₂ in a hydrophobic area extending to the hydrophobic plateau. The pathogenic mutation S163R disrupts this hydrogen bonding and positively charges these hydrophobic areas. Thus, our analysis provides insights into the structural basis of the L-ORMD disease mechanism.

PubMed: 22892318
DOI: 10.1016/j.jsb.2012.07.011

Experimental method

X-RAY DIFFRACTION (1.337 Å)