View source for 2a01

[[Image:2a01.gif|left|200px]]<br />
<applet load="2a01" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="2a01, resolution 2.40&Aring;" />
'''Crystal Structure of Lipid-free Human Apolipoprotein A-I'''<br />

==Overview==
Despite three decades of extensive studies on human apolipoprotein A-I, (apoA-I), the major protein component in high-density lipoproteins, the, molecular basis for its antiatherogenic function is elusive, in part, because of lack of a structure of the full-length protein. We describe, here the crystal structure of lipid-free apoA-I at 2.4 A. The structure, shows that apoA-I is comprised of an N-terminal four-helix bundle and two, C-terminal helices. The N-terminal domain plays a prominent role in, maintaining its lipid-free conformation, indicating that mutants with, truncations in this region form inadequate models for explaining, functional properties of apoA-I. A model for transformation of the, lipid-free conformation to the high-density lipoprotein-bound form follows, from an analysis of solvent-accessible hydrophobic patches on the surface, of the structure and their proximity to the hydrophobic core of the, four-helix bundle. The crystal structure of human apoA-I displays a, hitherto-unobserved array of positively and negatively charged areas on, the surface. Positioning of the charged surface patches relative to, hydrophobic regions near the C terminus of the protein offers insights, into its interaction with cell-surface components of the reverse, cholesterol transport pathway and antiatherogenic properties of this, protein. This structure provides a much-needed structural template for, exploration of molecular mechanisms by which human apoA-I ameliorates, atherosclerosis and inflammatory diseases.

==Disease==
Known diseases associated with this structure: Amyloidosis, 3 or more types OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107680 107680]], ApoA-I and apoC-III deficiency, combined OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107680 107680]], Corneal clouding, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107680 107680]], Hypertriglyceridemia, one form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107680 107680]], Hypoalphalipoproteinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107680 107680]]

==About this Structure==
2A01 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with AC9 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2A01 OCA]. 

==Reference==
Crystal structure of human apolipoprotein A-I: insights into its protective effect against cardiovascular diseases., Ajees AA, Anantharamaiah GM, Mishra VK, Hussain MM, Murthy HM, Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2126-31. Epub 2006 Feb 1. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16452169 16452169]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Ajees, A.A.]]
[[Category: Anantharamaiah, G.M.]]
[[Category: Hussain, M.M.]]
[[Category: Mishra, V.K.]]
[[Category: Murthy, K.H.M.]]
[[Category: AC9]]
[[Category: four-helix bundle]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:43:56 2007''