SASDDC6: Small glutamine-rich tetratricopeptide repeat-containing protein ...

Basic information

Entry

Database: SASBDB / ID: SASDDC6

Sample

Small glutamine-rich tetratricopeptide repeat-containing protein alpha (N-terminal-TPR domains; SGTA_NT)

• Small glutamine-rich tetratricopeptide repeat-containing protein alpha Nterminal-TPR domains (protein), SGTA_NT-TPR, Homo sapiens

Function / homology

Function:

: / TRC complex / positive regulation of ERAD pathway / tail-anchored membrane protein insertion into ER membrane / post-translational protein targeting to endoplasmic reticulum membrane / positive regulation of ubiquitin-dependent protein catabolic process / BAT3 complex binding / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / : / negative regulation of ubiquitin-dependent protein catabolic process / : / molecular adaptor activity / membrane / identical protein binding / nucleus / cytosol / cytoplasm

Domain/homology:

SGTA, homodimerisation domain / Homodimerisation domain of SGTA / : / Tetratricopeptide repeat 1 / Tetratricopeptide repeat / Tetratricopeptide repeat / TPR repeat region circular profile. / TPR repeat profile. / Tetratricopeptide repeats / Tetratricopeptide repeat / Tetratricopeptide-like helical domain superfamily

Component:

Small glutamine-rich tetratricopeptide repeat-containing protein alpha

• Biological species: Homo sapiens (human)
• Citation: Journal: BMC Biol / Year: 2018; Title: Structural complexity of the co-chaperone SGTA: a conserved C-terminal region is implicated in dimerization and substrate quality control.; Authors: Santiago Martínez-Lumbreras / Ewelina M Krysztofinska / Arjun Thapaliya / Alessandro Spilotros / Dijana Matak-Vinkovic / Enrico Salvadori / Peristera Roboti / Yvonne Nyathi / Janina H Muench / Maxie M Roessler / Dmitri I Svergun / Stephen High / Rivka L Isaacson / ; Abstract: BACKGROUND: Protein quality control mechanisms are essential for cell health and involve delivery of proteins to specific cellular compartments for recycling or degradation. In particular, stray hydrophobic proteins are captured in the aqueous cytosol by a co-chaperone, the small glutamine-rich, tetratricopeptide repeat-containing protein alpha (SGTA), which facilitates the correct targeting of tail-anchored membrane proteins, as well as the sorting of membrane and secretory proteins that mislocalize to the cytosol and endoplasmic reticulum-associated degradation. Full-length SGTA has an unusual elongated dimeric structure that has, until now, evaded detailed structural analysis. The C-terminal region of SGTA plays a key role in binding a broad range of hydrophobic substrates, yet in contrast to the well-characterized N-terminal and TPR domains, there is a lack of structural information on the C-terminal domain. In this study, we present new insights into the conformation and organization of distinct domains of SGTA and show that the C-terminal domain possesses a conserved region essential for substrate processing in vivo.; RESULTS: We show that the C-terminal domain region is characterized by α-helical propensity and an intrinsic ability to dimerize independently of the N-terminal domain. Based on the properties of different regions of SGTA that are revealed using cell biology, NMR, SAXS, Native MS, and EPR, we observe that its C-terminal domain can dimerize in the full-length protein and propose that this reflects a closed conformation of the substrate-binding domain.; CONCLUSION: Our results provide novel insights into the structural complexity of SGTA and provide a new basis for mechanistic studies of substrate binding and release at the C-terminal region.

Contact author

• Rivka Isaacson (King's College London)

Models

Sample

• Sample: Name: Small glutamine-rich tetratricopeptide repeat-containing protein alpha (N-terminal-TPR domains; SGTA_NT); Specimen concentration: 0.60-4.50
• Buffer: Name: 10 mM potassium phosphate, 100 mM NaCl / pH: 6

Entity #1056

Name: SGTA_NT-TPR / Type: protein
Description: Small glutamine-rich tetratricopeptide repeat-containing protein alpha Nterminal-TPR domains
Formula weight: 23.592 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: O43765
Sequence:

GSMDNKKRLA YAIIQFLHDQ LRHGGLSSDA QESLEVAIQC LETAFGVTVE DSDLALPQTL PEIFEAAATG KEMPQDLRSP ARTPPSEEDS AEAERLKTEG NEQMKVENFE AAVHFYGKAI ELNPANAVYF CNRAAAYSKL GNYAGAVQDC ERAICIDPAY SKAYGRMGLA LSSLNKHVEA VAYYKKALEL DPDNETYKSN LKIAELKLRE APSPT

Experimental information

• Beam: Instrument name: PETRA III EMBL P12 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.124 Å / Dist. spec. to detc.: 3 mm
• Detector: Name: Pilatus 2M

Scan

Title: Small glutamine-rich tetratricopeptide repeat-containing protein alpha (N-terminal-TPR domains; SGTA_NT)
Measurement date: Jun 5, 2015 / Cell temperature: 25 °C / Exposure time: 0.045 sec. / Number of frames: 20 / Unit: 1/nm /

	Min	Max
Q	0.027	4.8012

Result

Experimental MW: 41 kDa / Type of curve: merged

	Guinier	Guinier error
Forward scattering, I0	10844	16
Radius of gyration, Rg	3.6 nm	0.1

	Min	Max
Guinier point	15	128