1YA9

Crystal Structure of the 22kDa N-Terminal Fragment of Mouse Apolipoprotein E

Summary for 1YA9

• Entry DOI: 10.2210/pdb1ya9/pdb
• Descriptor: Apolipoprotein E (2 entities in total)
• Functional Keywords: apolipoprotein e, ldl receptor binding, lipid transport
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 21052.61

Authors

Peters-Libeu, C.A.,Rutenber, E.,Newhouse, Y.,Hatters, D.M.,Weisgraber, K.H. (deposition date: 2004-12-17, release date: 2005-06-07, Last modification date: 2024-02-14)

Primary citation

Hatters, D.M.,Peters-Libeu, C.A.,Weisgraber, K.H.
Engineering conformational destabilization into mouse apolipoprotein E. A model for a unique property of human apolipoprotein E4
J.Biol.Chem., 280:26477-26482, 2005

PubMed Abstract: Apolipoprotein (apo) E4 is a major risk factor for Alzheimer and cardiovascular diseases. ApoE4 differs from the two other common isoforms (apoE2 and apoE3) by its lower resistance to denaturation and greater propensity to form partially folded intermediates. As a first step to determine the importance of stability differences in vivo, we reengineered a partially humanized variant of the amino-terminal domain of mouse apoE (T61R mouse apoE) to acquire a destabilized conformation like that of apoE4. For this process, we determined the crystal structure of wild-type mouse apoE, which, like apoE4, forms a four-helix bundle, and identified two structural differences in the turn between helices 2 and 3 and in the middle of helix 3 as potentially destabilizing sites. Introducing mutations G83T and N113G at these sites destabilized the mouse apoE conformation. The mutant mouse apoE more rapidly remodeled phospholipid than T61R mouse apoE, which supports the hypothesis that a destabilized conformation promotes apoE4 lipid binding.

PubMed: 15890642
DOI: 10.1074/jbc.M503910200

Experimental method

X-RAY DIFFRACTION (2.09 Å)