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Tyrosine residues mediate fibril formation in a dynamic light chain dimer interface

, : Tyrosine residues mediate fibril formation in a dynamic light chain dimer interface. Journal of Biological Chemistry 287(33): 27997-28006

Light chain amyloidosis is an incurable protein misfolding disease where monoclonal immunoglobulin light chains misfold and deposit as amyloid fibrils, causing organ failure and death. Previously, we determined that amyloidogenic light chains AL-09 and AL-103 do not form fibrils at pH 10 (tyrosine pK(a)). There are three tyrosine residues (32, 91, and 96) clustered in the dimer interface, interacting differently in the two light chain proteins due to their two different dimer conformations. These tyrosines may be ionized at pH 10, causing repulsion and inhibiting fibril formation. Here, we characterize single and double Tyr-to-Phe mutations in AL-09 and AL-103. All AL-09 Tyr-to-Phe mutants form fibrils at pH 10, whereas none of the AL-103 mutants form fibrils at pH 10. NMR studies suggest that although both AL-09 and AL-103 present conformational heterogeneity, only AL-09 favors dimer conformations where tyrosine residues mediate crucial interactions for amyloid formation.


PMID: 22740699

DOI: 10.1074/jbc.M112.362921

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Ivanov, I.P.; Grozev, G.; Dimitrov, G., 1982: The effect of vacuum level in machine milking of cows. Within the limits defined (320-500 mm Hg) the vacuum level had no effect on the quantity of milk obtained. When the vacuum fell below the lower limit incomplete milking resulted, while a vacuum above the upper limit predisposed animals to mastitis...

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Basu, T.K.; Dickerson, J.W.; Parke, D.V., 1975: Effect of protein/energy nutrition on rat plasma corticosteroids and liver microsomal hydroxylase activity. Male Wistar rats 24 days old were in 3 groups and fed on a control diet containing 210 g/kg protein to appetite; a low-protein diet of the stock diet diluted with starch to contain 70 g/kg protein, to appetite; or an amount of stock diet containin...

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Smith, T.W.; Remijan, P.W.; Remijan, W.; Kolder, H.E.; Snyder, J., 1979: A new test of visual acuity using a holographic phase grating and a laser. A new visual acuity testing device is able to determine a specific visual acuity of the retina even in the presence of opacities of the ocular media, such as a cataract. This is achieved by forming two spatially coherent, quasimonochromatic point...

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Whyburn, G.T., 1961: Compressibility And Uniform Convergence. Proceedings of the National Academy of Sciences of the United States of America 47(11): 1843-1847