ERRATUM: Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation

نویسندگان

  • Luke A. Miles
  • Gabriela A. N. Crespi
  • Larissa Doughty
  • Michael W. Parker
چکیده

Bapineuzumab is a humanized antibody developed by Pfizer and Johnson & Johnson targeting the amyloid (Aβ) plaques that underlie Alzheimer's disease neuropathology. Here we report the crystal structure of a Fab-Aβ peptide complex that reveals Bapineuzumab surprisingly captures Aβ in a monomeric helical conformation at the N-terminus. Microscale thermophoresis suggests that the Fab binds soluble Aβ(1-40) with a K(D) of 89 (±9) nM. The structure explains the antibody's exquisite selectivity for particular Aβ species and why it cannot recognize N-terminally modified or truncated Aβ peptides.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

P135: The Role of Amyloid Beta-Peptides and Tau Protein in Alzheimer\'s Disease

Alzheimer's desease is the most common age-related neurodegenerative disorder, and cognitive problems such as defects in learning and memory are of its symptoms.  Among the factors involved in the pathogenesis of the disease are biochemical disorders in protein production, oxidative stress, decreased acetylcholine secretion and inflammation of the brain tissue. Extra-neuronal accumulation ...

متن کامل

NMR structure of the water soluble Aβ17–34 peptide

Alzheimer's disease is the most common neurodegenerative disorder in the world. Its most significant symptoms are memory loss and decrease in cognition. Alzheimer's disease is characterized by aggregation of two proteins in the brain namely Aβ (amyloid β) and tau. Recent evidence suggests that the interaction of soluble Aβ with nAChR (nicotinic acetylcholine receptors) contributes to disease pr...

متن کامل

Nicotine inhibits amyloid formation by the beta-peptide.

The 42-residues beta-(1-42) peptide is the major protein component of amyloid plaque cores in Alzheimer's disease. In aqueous solution at physiological pH, the synthetic beta-(1-42) peptide readily aggregates and precipitates as oligomeric beta-sheet structures, a process that occurs during amyloid formation in Alzheimer's disease. Using circular dichroism (CD) and ultraviolet spectroscopic tec...

متن کامل

Interprotofilament interactions between Alzheimer's Abeta1-42 peptides in amyloid fibrils revealed by cryoEM.

Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of amyloid plaques in the brain. This amyloid primarily contains amyloid-beta (Abeta), a 39- to 43-aa peptide derived from the proteolytic cleavage of the endogenous amyloid precursor protein. The 42-residue-length Abeta peptide (Abeta(1-42)), the most abundant Abeta peptide found in plaques, has a much greate...

متن کامل

The Effect of Endurance Training on the Expression of PRDX6 and KAT2B Genes in Hippocampus of Beta Amyloid-Induced Rat Model of Alzheimer's Disease: An Experimental Study

Background and Objectives: Alzheimer's disease is the most common form of dementia. KAT2B (Lysine Acetyltransferase 2B) is a mitochondrial protein known as mitochondria clearing control organ by mitophagy. PRDX6 (Peroxiredoxin 6) is a key regulator of mitophagy and plays a critical role in maintaining mitochondrial ROS (Reactive oxygen species) homeostasis. Therefore, the purpose of this study ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2013