SASDGX4: Aryl-hydrocarbon-interacting protein-like 1 (Aryl-hydrocarbon-int...

Basic information

Entry

Database: SASBDB / ID: SASDGX4

Sample

Aryl-hydrocarbon-interacting protein-like 1

• Aryl-hydrocarbon-interacting protein-like 1(1-316) (protein), AIPL1, Homo sapiens

Function / homology

Function:

farnesylated protein binding / regulation of opsin-mediated signaling pathway / protein farnesylation / phototransduction, visible light / retina homeostasis / visual perception / photoreceptor inner segment / peptidyl-prolyl cis-trans isomerase activity / unfolded protein binding / nuclear speck / apoptotic process / negative regulation of apoptotic process / nucleoplasm / nucleus / cytosol / cytoplasm

Domain/homology:

AIP/AIPL1 / Peptidyl-prolyl cis-trans isomerase domain superfamily / TPR repeat region circular profile. / Tetratricopeptide repeats / Tetratricopeptide repeat / Tetratricopeptide-like helical domain superfamily

Component:

Aryl-hydrocarbon-interacting protein-like 1

• Biological species: Homo sapiens (human)
• Citation: Journal: J Biol Chem / Year: 2019; Title: Interaction of the tetratricopeptide repeat domain of aryl hydrocarbon receptor-interacting protein-like 1 with the regulatory Pγ subunit of phosphodiesterase 6.; Authors: Ravi P Yadav / Kimberly Boyd / Liping Yu / Nikolai O Artemyev / ; Abstract: Phosphodiesterase-6 (PDE6) is key to both phototransduction and health of rods and cones. Proper folding of PDE6 relies on the chaperone activity of aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1), and mutations in both PDE6 and AIPL1 can cause a severe form of blindness. Although AIPL1 and PDE6 are known to interact via the FK506-binding protein domain of AIPL1, the contribution of the tetratricopeptide repeat (TPR) domain of AIPL1 to its chaperone function is poorly understood. Here, we demonstrate that AIPL1-TPR interacts specifically with the regulatory Pγ subunit of PDE6. Use of NMR chemical shift perturbation (CSP) mapping technique revealed the interface between the C-terminal portion of Pγ and AIPL1-TPR. Our solution of the crystal structure of the AIPL1-TPR domain provided additional information, which together with the CSP data enabled us to generate a model of this interface. Biochemical analysis of chimeric AIPL1-AIP proteins supported this model and also revealed a correlation between the affinity of AIPL1-TPR for Pγ and the ability of Pγ to potentiate the chaperone activity of AIPL1. Based on these results, we present a model of the larger AIPL1-PDE6 complex. This supports the importance of simultaneous interactions of AIPL1-FK506-binding protein with the prenyl moieties of PDE6 and AIPL1-TPR with the Pγ subunit during the folding and/or assembly of PDE6. This study sheds new light on the versatility of TPR domains in protein folding by describing a novel TPR-protein binding partner, Pγ, and revealing that this subunit imparts AIPL1 selectivity for its client.

Contact author

• Ravi Prakash Yadav (University of Iowa Carver College of Medicine, Iowa, USA)

Models

Sample

• Sample: Name: Aryl-hydrocarbon-interacting protein-like 1 / Specimen concentration: 10 mg/ml
• Buffer: Name: 50 mM Tris, 100 mM NaCl, 2.5 % glycerol and 6 mM DTT / pH: 7.5

Entity #1870

Name: AIPL1 / Type: protein
Description: Aryl-hydrocarbon-interacting protein-like 1(1-316)
Formula weight: 37.105 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q9NZN9
Sequence:

SHMDAALLLN VEGVKKTILH GGTGELPNFI TGSRVIFHFR TMKCDEERTV IDDSRQVGQP MHIIIGNMFK LEVWEILLTS MRVHEVAEFW CDTIHTGVYP ILSRSLRQMA QGKDPTEWHV HTCGLANMFA YHTLGYEDLD ELQKEPQPLV FVIELLQVDA PSDYQRETWN LSNHEKMKAV PVLHGEGNRL FKLGRYEEAS SKYQEAIICL RNLQTKEKPW EVQWLKLEKM INTLILNYCQ CLLKKEEYYE VLEHTSDILR HHPGIVKAYY VRARAHAEVW NEAEAKADLQ KVLELEPSMQ KAVRRELRLL ENRMAEKQ

Experimental information

• Beam: Instrument name: Advanced Photon Source (APS), Argonne National Laboratory BioCAT 18ID; City: Lemont, IL / 国: USA / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.1033 Å / Dist. spec. to detc.: 3.5 mm
• Detector: Name: Pilatus3 X 1M / Pixsize x: 0.172 mm

Scan

Title: Aryl-hydrocarbon-interacting protein-like 1 / Measurement date: Jul 17, 2018 / Exposure time: 0.5 sec. / Unit: 1/A /

	Min	Max
Q	0.0061	0.3854

Distance distribution function P(R)

Sofotware P(R): GNOM 4.5a / Number of points: 481 /

	Min	Max
Q	0.01452	0.3075
P(R) point	28	508
R	0	90.99

Result

Type of curve: sec /

	Experimental	Porod
MW	37 kDa	37 kDa
Volume	-	60 nm3

	P(R)	Guinier	Guinier error
Forward scattering, I0	57.11	56.86	0.16
Radius of gyration, Rg	2.66 nm	2.599 nm	0.105

	Min	Max
D	-	9.1
Guinier point	11	144