SASDDN6: Human stress-inducible heat shock 70 kDa protein 1, Hsp70 (Hspa1a...

基本情報

• 登録情報: データベース: SASBDB / ID: SASDDN6

試料

Human stress-inducible heat shock 70 kDa protein 1, Hsp70 (Hspa1a) T204A mutant dimer, in the presence of ATP

• Heat shock 70 kDa protein 1 (protein), HSPA1A_T204A, Homo sapiens

機能・相同性

分子機能:

positive regulation of endoribonuclease activity / denatured protein binding / cellular heat acclimation / negative regulation of inclusion body assembly / death receptor agonist activity / Viral RNP Complexes in the Host Cell Nucleus / C3HC4-type RING finger domain binding / positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway / positive regulation of microtubule nucleation / ATP-dependent protein disaggregase activity / misfolded protein binding / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / positive regulation of tumor necrosis factor-mediated signaling pathway / regulation of mitotic spindle assembly / lysosomal transport / transcription regulator inhibitor activity / aggresome / cellular response to steroid hormone stimulus / mRNA catabolic process / chaperone cofactor-dependent protein refolding / regulation of protein ubiquitination / HSF1-dependent transactivation / response to unfolded protein / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / chaperone-mediated protein complex assembly / cellular response to unfolded protein / Regulation of HSF1-mediated heat shock response / Attenuation phase / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / ATP metabolic process / inclusion body / heat shock protein binding / negative regulation of protein ubiquitination / protein folding chaperone / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / centriole / positive regulation of erythrocyte differentiation / positive regulation of RNA splicing / positive regulation of interleukin-8 production / AUF1 (hnRNP D0) binds and destabilizes mRNA / G protein-coupled receptor binding / ATP-dependent protein folding chaperone / negative regulation of transforming growth factor beta receptor signaling pathway / PKR-mediated signaling / negative regulation of cell growth / histone deacetylase binding / transcription corepressor activity / disordered domain specific binding / unfolded protein binding / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of NF-kappaB transcription factor activity / virus receptor activity / cellular response to oxidative stress / cellular response to heat / protein refolding / vesicle / ficolin-1-rich granule lumen / blood microparticle / protein stabilization / receptor ligand activity / nuclear speck / cadherin binding / ribonucleoprotein complex / negative regulation of cell population proliferation / signaling receptor binding / focal adhesion / centrosome / ubiquitin protein ligase binding / Neutrophil degranulation / positive regulation of gene expression / negative regulation of apoptotic process / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / enzyme binding / endoplasmic reticulum / ATP hydrolysis activity / protein-containing complex / mitochondrion / RNA binding / extracellular space / extracellular exosome / extracellular region / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm

ドメイン・相同性:

Heat shock hsp70 proteins family signature 2. / Heat shock hsp70 proteins family signature 1. / Heat shock hsp70 proteins family signature 3. / Heat shock protein 70, conserved site / Heat shock protein 70kD, peptide-binding domain superfamily / Heat shock protein 70 family / Hsp70 protein / Heat shock protein 70kD, C-terminal domain superfamily / ATPase, nucleotide binding domain

構成要素:

Heat shock 70 kDa protein 1A

• 生物種: Homo sapiens (ヒト)
• 引用: ジャーナル: Mol Cell Proteomics / 年: 2019; タイトル: Human Stress-inducible Hsp70 Has a High Propensity to Form ATP-dependent Antiparallel Dimers That Are Differentially Regulated by Cochaperone Binding.; 著者: Filip Trcka / Michal Durech / Pavla Vankova / Josef Chmelik / Veronika Martinkova / Jiri Hausner / Alan Kadek / Julien Marcoux / Tomas Klumpler / Borivoj Vojtesek / Petr Muller / Petr Man / ; 要旨: Eukaryotic protein homeostasis (proteostasis) is largely dependent on the action of highly conserved Hsp70 molecular chaperones. Recent evidence indicates that, apart from conserved molecular allostery, Hsp70 proteins have retained and adapted the ability to assemble as functionally relevant ATP-bound dimers throughout evolution. Here, we have compared the ATP-dependent dimerization of DnaK, human stress-inducible Hsp70, Hsc70 and BiP Hsp70 proteins, showing that their dimerization propensities differ, with stress-inducible Hsp70 being predominantly dimeric in the presence of ATP. Structural analyses using hydrogen/deuterium exchange mass spectrometry, native electrospray ionization mass spectrometry and small-angle X-ray scattering revealed that stress-inducible Hsp70 assembles in solution as an antiparallel dimer with the intermolecular interface closely resembling the ATP-bound dimer interfaces captured in DnaK and BiP crystal structures. ATP-dependent dimerization of stress-inducible Hsp70 is necessary for its efficient interaction with Hsp40, as shown by experiments with dimerization-deficient mutants. Moreover, dimerization of ATP-bound Hsp70 is required for its participation in high molecular weight protein complexes detected , supporting its functional role As human cytosolic Hsp70 can interact with tetratricopeptide repeat (TPR) domain containing cochaperones, we tested the interaction of Hsp70 ATP-dependent dimers with Chip and Tomm34 cochaperones. Although Chip associates with intact Hsp70 dimers to form a larger complex, binding of Tomm34 disrupts the Hsp70 dimer and this event plays an important role in Hsp70 activity regulation. In summary, this study provides structural evidence of robust ATP-dependent antiparallel dimerization of human inducible Hsp70 protein and suggests a novel role of TPR domain cochaperones in multichaperone complexes involving Hsp70 ATP-bound dimers.

登録者

• Tomas Klumpler (CEITEC - Central European Institute of Technology, Masaryk University)

モデル

• モデル #2029: ; タイプ: atomic / カイ2乗値: 1.150 / P-value: 0.489949; Omokage検索でこの集合体の類似形状データを探す (詳細)

試料

• 試料: 名称: Human stress-inducible heat shock 70 kDa protein 1, Hsp70 (Hspa1a) T204A mutant dimer, in the presence of ATP; 試料濃度: 2.5 mg/ml
• バッファ: 名称: 50mM HEPES, 150mM KCH3COO, 2mM MgCl2 / pH: 7.5

要素 #1080

名称: HSPA1A_T204A / タイプ: protein / 記述: Heat shock 70 kDa protein 1 / 分子量: 73.74 / 分子数: 2 / 由来: Homo sapiens / 参照: UniProt: P0DMV8
配列:

MSYYHHHHHH LESTSLYKKA GFGSENLYFQ SMAKAAAIGI DLGTTYSCVG VFQHGKVEII ANDQGNRTTP SYVAFTDTER LIGDAAKNQV ALNPQNTVFD AKRLIGRKFG DPVVQSDMKH WPFQVINDGD KPKVQVSYKG ETKAFYPEEI SSMVLTKMKE IAEAYLGYPV TNAVITVPAY FNDSQRQATK DAGVIAGLNV LRIINEPTAA AIAYGLDRTG KGERNVLIFD LGGGAFDVSI LTIDDGIFEV KATAGDTHLG GEDFDNRLVN HFVEEFKRKH KKDISQNKRA VRRLRTACER AKRTLSSSTQ ASLEIDSLFE GIDFYTSITR ARFEELCSDL FRSTLEPVEK ALRDAKLDKA QIHDLVLVGG STRIPKVQKL LQDFFNGRDL NKSINPDEAV AYGAAVQAAI LMGDKSENVQ DLLLLDVAPL SLGLETAGGV MTALIKRNST IPTKQTQIFT TYSDNQPGVL IQVYEGERAM TKDNNLLGRF ELSGIPPAPR GVPQIEVTFD IDANGILNVT ATDKSTGKAN KITITNDKGR LSKEEIERMV QEAEKYKAED EVQRERVSAK NALESYAFNM KSAVEDEGLK GKISEADKKK VLDKCQEVIS WLDANTLAEK DEFEHKRKEL EQVCNPIISG LYQGAGGPGP GGFGAQGPKG GSGSGPTIEE VD

実験情報

• ビーム: 設備名称: CEITEC Rigaku BioSAXS-1000 / 地域: Brno / 国: Czech Republic / 線源: X-ray in house / 波長: 0.154 Å / スペクトロメータ・検出器間距離: 0.48 mm
• 検出器: 名称: Pilatus 100K / Pixsize x: 172 mm

スキャン

タイトル: Human stress-inducible heat shock 70 kDa protein 1, Hsp70 (Hspa1a) T204A mutant dimer, in the presence of ATP
測定日: 2018年2月20日 / 保管温度: 4 °C / セル温度: 4 °C / 照射時間: 3600 sec. / 単位: 1/A /

	Min	Max
Q	0.0138	0.6314

距離分布関数 P(R)

ソフトウェア P(R): GNOM 5.0 / ポイント数: 130 /

	Min	Max
Q	0.0137969	0.199503
P(R) point	1	130
R	0	115.6

結果

カーブのタイプ: single_conc /

	実験値	Porod
分子量	148 kDa	155 kDa
体積	-	248 nm3

	P(R)	P(R) error	Guinier	Guinier error
前方散乱 I0	0.7457	0.0058	0.76	0.011
慣性半径, Rg	3.97 nm	0.2	4.01 nm	0.077

	Min	Max
D	-	11.56
Guinier point	2	14