A type III complement factor D deficiency: Structural insights for inhibition of the alternative pathway

• Published in: Journal of allergy and clinical immunology Vol. 142; no. 1; pp. 311 - 314.e6
• Main Authors: Sng, Christopher C.T., O'Byrne, Sorcha, Prigozhin, Daniil M., Bauer, Matthias R., Harvey, Jennifer C., Ruhle, Michelle, Challis, Ben G., Lear, Sara, Roberts, Lee D., Workman, Sarita, Janowitz, Tobias, Magiera, Lukasz, Doffinger, Rainer, Buckland, Matthew S., Jodrell, Duncan J., Semple, Robert K., Wilson, Timothy J., Modis, Yorgo, Thaventhiran, James E.D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2018; Elsevier Limited; Mosby
• Subjects: Alternative pathway; Complement factor D; Complement Factor D - chemistry; Complement Factor D - deficiency; Complement Factor D - genetics; Complement Pathway, Alternative; Female; Hereditary Complement Deficiency Diseases; Humans; Immunologic Deficiency Syndromes - genetics; Inflammatory diseases; Macular degeneration; Male; Metabolism; Mutation; Pedigree; Protein Conformation; Simulation; Young Adult

Conversely, in both mutant simulations, the distance remained larger, consistent with His41 pointing away from the active site. [...]in addition to disruption of key FB-binding residues, mutations R176P and R176A appear to stabilize the self-inhibited conformation of free FD. Overactivation of AP is...