| Structural highlights
Disease
[LDLR_HUMAN] Defects in LDLR are the cause of familial hypercholesterolemia (FH) [MIM:143890]; a common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [:][32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43]
Function
[LDLR_HUMAN] Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.
Publication Abstract from PubMed
Vesicular stomatitis virus (VSV) is an oncolytic rhabdovirus and its glycoprotein G is widely used to pseudotype other viruses for gene therapy. Low-density lipoprotein receptor (LDL-R) serves as a major entry receptor for VSV. Here we report two crystal structures of VSV G in complex with two distinct cysteine-rich domains (CR2 and CR3) of LDL-R, showing that their binding sites on G are identical. We identify two basic residues on G, which are essential for its interaction with CR2 and CR3. Mutating these residues abolishes VSV infectivity even though VSV can use alternative receptors, indicating that all VSV receptors are members of the LDL-R family. Collectively, our data suggest that VSV G has specifically evolved to interact with receptor CR domains. These structural insights into the interaction between VSV G and host cell receptors provide a basis for the design of recombinant viruses with an altered tropism.
Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein.,Nikolic J, Belot L, Raux H, Legrand P, Gaudin Y, A Albertini A Nat Commun. 2018 Mar 12;9(1):1029. doi: 10.1038/s41467-018-03432-4. PMID:29531262[44]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Nikolic J, Belot L, Raux H, Legrand P, Gaudin Y, A Albertini A. Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein. Nat Commun. 2018 Mar 12;9(1):1029. doi: 10.1038/s41467-018-03432-4. PMID:29531262 doi:https://dx.doi.org/10.1038/s41467-018-03432-4
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