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7lfa

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Fab 3B6 bound to ApoL1 NTD

Structural highlights

7lfa is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.857Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

APOL1_HUMAN Genetic steroid-resistant nephrotic syndrome. The disease is caused by variants affecting the gene represented in this entry.

Function

APOL1_HUMAN May play a role in lipid exchange and transport throughout the body. May participate in reverse cholesterol transport from peripheral cells to the liver.

Publication Abstract from PubMed

Apolipoprotein L1 (ApoL1) is a circulating innate immunity protein protecting against trypanosome infection. However, two ApoL1 coding variants are associated with a highly increased risk of chronic kidney disease. Here we present X-ray and NMR structures of the N-terminal domain (NTD) of ApoL1 and of its closest relative ApoL2. In both proteins, four of the five NTD helices form a four-helix core structure which is different from the classical four-helix bundle and from the pore-forming domain of colicin A. The reactivity with a conformation-specific antibody and structural models predict that this four-helix motif is also present in the NTDs of ApoL3 and ApoL4, suggesting related functions within the small ApoL family. The long helix 5 of ApoL1 is conformationally flexible and contains the BH3-like region. This BH3-like alpha-helix resembles true BH3 domains only in sequence and structure but not in function, since it does not bind to the pro-survival members of the Bcl-2 family, suggesting a Bcl-2-independent role in cytotoxicity. These findings should expedite a more comprehensive structural and functional understanding of the ApoL immune protein family.

Structures of the ApoL1 and ApoL2 N-terminal domains reveal a non-classical four-helix bundle motif.,Ultsch M, Holliday MJ, Gerhardy S, Moran P, Scales SJ, Gupta N, Oltrabella F, Chiu C, Fairbrother W, Eigenbrot C, Kirchhofer D Commun Biol. 2021 Jul 27;4(1):916. doi: 10.1038/s42003-021-02387-5. PMID:34316015^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ultsch M, Holliday MJ, Gerhardy S, Moran P, Scales SJ, Gupta N, Oltrabella F, Chiu C, Fairbrother W, Eigenbrot C, Kirchhofer D. Structures of the ApoL1 and ApoL2 N-terminal domains reveal a non-classical four-helix bundle motif. Commun Biol. 2021 Jul 27;4(1):916. doi: 10.1038/s42003-021-02387-5. PMID:34316015 doi:http://dx.doi.org/10.1038/s42003-021-02387-5