有哪些信誉好的足球投注网站mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with al amyloidosis在特定结构突变的区域免疫球蛋白轻链与游离轻链al淀粉样变患者的水平.pdfVIP
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mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with al amyloidosis在特定结构突变的区域免疫球蛋白轻链与游离轻链al淀粉样变患者的水平
Mutations in Specific Structural Regions of Immunoglobulin Light Chains Are Associated with Free Light Chain Levels in Patients with AL Amyloidosis 1 1 2 3 4 Tanya L. Poshusta , Laura A. Sikkink , Nelson Leung , Raynell J. Clark , Angela Dispenzieri , Marina Ramirez-Alvarado1* 1 Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America, 2 Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America, 3 Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America, 4 Division of Hematology, Mayo Clinic, Rochester, Minnesota, United States of America Abstract Background: The amyloidoses are protein misfolding diseases characterized by the deposition of amyloid that leads to cell death and tissue degeneration. In immunoglobulin light chain amyloidosis (AL), each patient has a unique monoclonal immunoglobulin light chain (LC) that forms amyloid deposits. Somatic mutations in AL LCs make these proteins less thermodynamically stable than their non-amyloidogenic counterparts, leading to misfolding and ultimately the formation of amyloid fibrils. We hypothesize that location rather than number of non-conservative mutations determines the amyloidogenicity of light chains. Methodology/Principal Findings: We performed sequence alignments on the variable domain of 50 k and 91 l AL light chains and calculated the number of non-conservative mutations over total number of patients for each secondary structure element in order to identify regions that accumulate non-conservative mutations. Among patients with AL, the levels o
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