wiki CD46: http://en.wikipedia.org/wiki/CD46
"CD46 complement regulatory protein, also known as CD46 (cluster of differentiation 46) and Membrane Cofactor Protein
, is a protein which in humans is encoded by the CD46 gene. CD46 is an inhibitory complement receptor."
so if defective CD46 is a problem, and it's a protein, could protein misfolding be the defect? investigating the structure of CD46... ow my brain...
Structure of the Extracellular Portion of CD46 Provides Insights into Its Interactions with Complement Proteins and Pathogenshttp://www.plospathogens.org/article/in ... at.1001122
"Common to all the proteins expressed from the RCA cluster is their modular construction, which is primarily based on concatenated short consensus repeats (SCR) . Each SCR module contains about 60 amino acids that fold into a compact β-barrel domain surrounded by flexible loops . While the modules display high sequence variability, they all contain four conserved cysteine residues that form two disulfide bridges at the top and bottom of the repeat. The number of repeats present in the members of the RCA family ranges from four in CD55 and CD46 to 30 in CD35. Many structures of fragments of RCA family members are known, and they exhibit significant diversity both in their loop structures and also in their interdomain orientation , . The four SCRs in CD46 constitute the bulk of its extracellular region. The repeats are connected to a short linker region rich in serines, threonines and prolines (STP region), a single membrane-spanning segment, and a cytoplasmic tail. Alternative splicing generates multiple isoforms of CD46 that all have identical N-terminal repeats but exhibit variation in the STP region and the cytoplasmic tail .
The crystal structure of the N-terminal two repeats, SCR1 and SCR2, of CD46 (CD46-2D) revealed essential features of this region, including a pronounced bend between the two repeats and significant flexibility at the interdomain interface . Although CD46-2D is heavily glycosylated, one side of the two-domain fragment was found to be entirely devoid of glycans. Subsequent crystal structures of CD46-2D in complex with the Adv fiber knob ,  and with the MV hemagglutinin  demonstrated that both viral attachment proteins bind to this glycan-free surface. In both cases, engagement by the virus leads to “straightening” of the CD46-2D protein into a linear conformation. Furthermore, both viral attachment proteins form contacts with CD46-2D that predominantly involve residues at the SCR1-SCR2 interface. The implications of the structural rearrangement of CD46 upon ligand binding are not understood."
here we are at membranes and tight junctions again...
A novel Role for the complement regulator CD46 in epithelial tight junction formation/regulationhttps://wao.confex.com/wao/2010isc/webp ... r1705.html
"...we found that CD46 interacts with E-cadherin and SPAK, both vital proteins in the maintenance of epithelial cell layer integrity. Mutations in either protein cause colon cancer or IBD, respectively. Further, we observed that CD46 regulates tight junctions and by this transepithelial resistance and paracellular permeability. Based on these data we hypothesize that complement/CD46 communicates with the E-cadherin/catenin network in epithelial cells (via interaction/activation of SPAK) and contributes to normal epithelial cell barrier integrity."
taking it back to some earlier thoughts (2008) i had on intestinal membrane integrity and zinc...general-discussion-f1/topic4968.html#p34958
Trace Elements in Human Health and Disease: An Update
The many functions of zinc in inflammatory conditions of the gastrointestinal tract
gastric diseases; inflammatory bowel disease; intestinal permeability; inflammation; zinc
A variety of inflammatory gastrointestinal diseases are associated with altered zinc metabolism or deficiency. Acute and chronic diarrheal disorders may cause deficiency because of increased losses, altered immunity or decreased absorption. When the small intestinal barrier is altered by inflammation, zinc supplementation may be beneficial not only in correcting the deficiency but also because it improves the small bowel mucosal capacity of absorbing water and electrolytes. Zinc is known to have antioxidant properties being a membrane stabilizer, scavenging reactive oxygen metabolites and regulating cytokine synthesis through the activation of transcription factors and this has relevant potential in inflammatory bowel diseases. Moreover, the element stimulates tissue healing and repair in experimental ulcers directly through promoting cell proliferation, protein synthesis and growth factors production and scavenging free radicals. Interest is growing in supplementary therapies with elements and vitamins but current research suggests great caution and to balance the benefits and dangers of uncontrolled administration, since zinc can also stimulate an increased acute phase response and this can exacerbate chronic relapsing diseases. Zinc plays an important role in inflammation. The metal has catalytic, co-catalytic and structural functions in many zinc-dependent enzymes of the body through the regulation of gene expression. Moreover, the involvement of zinc finger proteins in the genetic expression of growth factors has been established. Zinc stabilizes cellular membranes especially interacting at the SH levels and preventing depolarization of phospholipids. The effects on cellular immunity and especially on the activity of serum thymulin and natural killer cells, T-lymphocyte proliferation and interleukin-2 production are also well-known. A growing body of evidence suggests a role for zinc in antioxidant defence systems. The metal has only one stable oxidation state (divalent) and is not affected by free radicals or oxidative stress. It may act as a scavenger of radical products through the synthesis of enzymes such as superoxide dismutase (SOD) and metallothionein (MT) or it may affect cytokine-activated transcription factors. J. Trace Elem. Exp. Med. 13:33-39, 2000. © 2000 Wiley-Liss, Inc.
i've posted elsewhere on zinc and protein misfolding, but it's going to take me a while to figure out if any of this hangs together...