SASDB38: Inactivated complement factor 1 (C1) (Complement C1q subcomponent...

基本情報

• 登録情報: データベース: SASBDB / ID: SASDB38

試料

Inactivated complement factor 1 (C1)

• Complement C1q subcomponent subunit C (protein), C1qc, Homo sapiens (plasma purified)
• Complement C1q subcomponent subunit B (protein), C1qb, Homo sapiens (plasma purified)
• Complement C1q subcomponent subunit A (protein), C1qa, Homo sapiens
• Complement C1r subcomponent (protein), C1r, Homo sapiens
• Complement C1s subcomponent (protein), C1s, Homo sapiens

機能・相同性

分子機能:

complement subcomponent C_overbar_1r_ / complement component C1 complex / complement component C1q complex / complement subcomponent C_overbar_1s_ / negative regulation of macrophage differentiation / synapse pruning / negative regulation of granulocyte differentiation / vertebrate eye-specific patterning / complement-mediated synapse pruning / molecular sequestering activity / collagen trimer / complement activation / zymogen activation / Classical antibody-mediated complement activation / neuron remodeling / Initial triggering of complement / serine-type peptidase activity / complement activation, classical pathway / Regulation of Complement cascade / astrocyte activation / microglial cell activation / synapse organization / cell-cell signaling / amyloid-beta binding / postsynapse / collagen-containing extracellular matrix / blood microparticle / immune response / serine-type endopeptidase activity / innate immune response / synapse / calcium ion binding / proteolysis / extracellular space / extracellular exosome / extracellular region / identical protein binding

ドメイン・相同性:

C1q domain / C1q domain / C1q domain profile. / Complement component C1q domain. / Peptidase S1A, complement C1r/C1S/mannan-binding / CUB domain / Domain first found in C1r, C1s, uEGF, and bone morphogenetic protein. / CUB domain / CUB domain profile. / Tumour necrosis factor-like domain superfamily / Spermadhesin, CUB domain superfamily / Collagen triple helix repeat / Collagen triple helix repeat (20 copies) / Sushi repeat (SCR repeat) / Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR) / Sushi/SCR/CCP domain / Sushi/CCP/SCR domain profile. / Sushi/SCR/CCP superfamily / Coagulation Factor Xa inhibitory site / EGF-type aspartate/asparagine hydroxylation site / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / Epidermal growth factor-like domain. / EGF-like domain signature 2. / EGF-like domain / Serine proteases, trypsin family, serine active site / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin domain profile. / Serine proteases, trypsin family, serine active site. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan

構成要素:

Complement C1r subcomponent / Complement C1q subcomponent subunit A / Complement C1q subcomponent subunit B / Complement C1q subcomponent subunit C / Complement C1s subcomponent

• 生物種: Homo sapiens (plasma purified); Homo sapiens (ヒト)
• 引用: ジャーナル: Proc Natl Acad Sci U S A / 年: 2017; タイトル: Structure and activation of C1, the complex initiating the classical pathway of the complement cascade.; 著者: Simon A Mortensen / Bjoern Sander / Rasmus K Jensen / Jan Skov Pedersen / Monika M Golas / Jens C Jensenius / Annette G Hansen / Steffen Thiel / Gregers R Andersen / ; 要旨: The complement system is an important antimicrobial and inflammation-generating component of the innate immune system. The classical pathway of complement is activated upon binding of the 774-kDa C1 complex, consisting of the recognition molecule C1q and the tetrameric protease complex C1rs, to a variety of activators presenting specific molecular patterns such as IgG- and IgM-containing immune complexes. A canonical model entails a C1rs with its serine protease domains tightly packed together in the center of C1 and an intricate intramolecular reaction mechanism for activation of C1r and C1s, induced upon C1 binding to the activator. Here, we show that the serine protease domains of C1r and C1s are located at the periphery of the C1rs tetramer both when alone or within the nonactivated C1 complex. Our structural studies indicate that the C1 complex adopts a conformation incompatible with intramolecular activation of C1, suggesting instead that intermolecular proteolytic activation between neighboring C1 complexes bound to a complement activating surface occurs. Our results rationalize how a multitude of structurally unrelated molecular patterns can activate C1 and suggests a conserved mechanism for complement activation through the classical and the related lectin pathway.

登録者

• Rasmus Jensen (Aarhus University, Aarhus, Denmark)

モデル

• モデル #923: ; タイプ: atomic / ソフトウェア: (CORALXL) / ダミー原子の半径: 1.90 A / 対称性: P2 / カイ2乗値: 2.34; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #924: ; タイプ: atomic / ソフトウェア: (CORALXL) / ダミー原子の半径: 1.90 A / 対称性: P2 / カイ2乗値: 2.44; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #1959: ; タイプ: atomic / ソフトウェア: (CORALXL) / ダミー原子の半径: 1.90 A / 対称性: P2 / カイ2乗値: 2.30; 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: Inactivated complement factor 1 (C1) / Entity id: 541 / 542 / 543 / 544 / 545
• バッファ: 名称: 50 mM EPPS, 145 mM NaCl, 3 mM CaCl2 / pH: 8.5

要素 #541

名称: C1qc / タイプ: protein / 記述: Complement C1q subcomponent subunit C / 分子量: 23.687 / 分子数: 6 / 由来: Homo sapiens (plasma purified) / 参照: UniProt: P02747
配列:

EDLCRAPDGK KGEAGRPGRR GRPGLKGEQG EPGAPGIRTG IQGLKGDQGE PGPSGNPGKV GYPGPSGPLG ARGIPGIKGT KGSPGNIKDQ PRPAFSAIRR NPPMGGNVVI FDTVITNQEE PYQNHSGRFV CTVPGYYYFT FQVLSQWEIC LSIVSSSRGQ VRRSLGFCDT TNKGLFQVVS GGMVLQLQQG DQVWVEKDPK KGHIYQGSEA DSVFSGFLIF PSA

要素 #542

名称: C1qb / タイプ: protein / 記述: Complement C1q subcomponent subunit B / 分子量: 23.742 / 分子数: 6 / 由来: Homo sapiens (plasma purified) / 参照: UniProt: P02746
配列:

QLSCTGPPAI PGIPGIPGTP GPDGQPGTPG IKGEKGLPGL AGDHGEFGEK GDPGIPGNPG KVGPKGPMGP KGGPGAPGAP GPKGESGDYK ATQKIAFSAT RTINVPLRRD QTIRFDHVIT NMNNNYEPRS GKFTCKVPGL YYFTYHASSR GNLCVNLMRG RERAQKVVTF CDYAYNTFQV TTGGMVLKLE QGENVFLQAT DKNSLLGMEG ANSIFSGFLL FPDMEA

要素 #543

名称: C1qa / タイプ: protein / 記述: Complement C1q subcomponent subunit A / 分子量: 23.687 / 分子数: 6 / 由来: Homo sapiens / 参照: UniProt: P02745
配列:

EDLCRAPDGK KGEAGRPGRR GRPGLKGEQG EPGAPGIRTG IQGLKGDQGE PGPSGNPGKV GYPGPSGPLG ARGIPGIKGT KGSPGNIKDQ PRPAFSAIRR NPPMGGNVVI FDTVITNQEE PYQNHSGRFV CTVPGYYYFT FQVLSQWEIC LSIVSSSRGQ VRRSLGFCDT TNKGLFQVVS GGMVLQLQQG DQVWVEKDPK KGHIYQGSEA DSVFSGFLIF PSA

要素 #544

名称: C1r / タイプ: protein / 記述: Complement C1r subcomponent / 分子量: 78.212 / 分子数: 2 / 由来: Homo sapiens / 参照: UniProt: P00736
配列:

SIPIPQKLFG EVTSPLFPKP YPNNFETTTV ITVPTGYRVK LVFQQFDLEP SEGCFYDYVK ISADKKSLGR FCGQLGSPLG NPPGKKEFMS QGNKMLLTFH TDFSNEENGT IMFYKGFLAY YQAVDLDECA SRSKSGEEDP QPQCQHLCHN YVGGYFCSCR PGYELQEDTH SCQAECSSEL YTEASGYISS LEYPRSYPPD LRCNYSIRVE RGLTLHLKFL EPFDIDDHQQ VHCPYDQLQI YANGKNIGEF CGKQRPPDLD TSSNAVDLLF FTDESGDSRG WKLRYTTEII KCPQPKTLDE FTIIQNLQPQ YQFRDYFIAT CKQGYQLIEG NQVLHSFTAV CQDDGTWHRA MPRCKIKDCG QPRNLPNGDF RYTTTMGVNT YKARIQYYCH EPYYKMQTRA GSRESEQGVY TCTAQGIWKN EQKGEKIPRC LPVCGKPVNP VEQRQRIIGG QKAKMGNFPW QVFTNIHGRG GGALLGDRWI LTAAHTLYPK EHEAQSNASL DVFLGHTNVE ELMKLGNHPI RRVSVHPDYR QDESYNFEGD IALLELENSV TLGPNLLPIC LPDNDTFYDL GLMGYVSGFG VMEEKIAHDL RFVRLPVANP QACENWLRGK NRMDVFSQNM FCAGHPSLKQ DACQGDSGGV FAVRDPNTDR WVATGIVSWG IGCSRGYGFY TKVLNYVDWI KKEMEEED

要素 #545

名称: C1s / タイプ: protein / 記述: Complement C1s subcomponent / 分子量: 74.886 / 分子数: 2 / 由来: Homo sapiens / 参照: UniProt: P09871
配列:

EPTMYGEILS PNYPQAYPSE VEKSWDIEVP EGYGIHLYFT HLDIELSENC AYDSVQIISG DTEEGRLCGQ RSSNNPHSPI VEEFQVPYNK LQVIFKSDFS NEERFTGFAA YYVATDINEC TDFVDVPCSH FCNNFIGGYF CSCPPEYFLH DDMKNCGVNC SGDVFTALIG EIASPNYPKP YPENSRCEYQ IRLEKGFQVV VTLRREDFDV EAADSAGNCL DSLVFVAGDR QFGPYCGHGF PGPLNIETKS NALDIIFQTD LTGQKKGWKL RYHGDPMPCP KEDTPNSVWE PAKAKYVFRD VVQITCLDGF EVVEGRVGAT SFYSTCQSNG KWSNSKLKCQ PVDCGIPESI ENGKVEDPES TLFGSVIRYT CEEPYYYMEN GGGGEYHCAG NGSWVNEVLG PELPKCVPVC GVPREPFEEK QRIIGGSDAD IKNFPWQVFF DNPWAGGALI NEYWVLTAAH VVEGNREPTM YVGSTSVQTS RLAKSKMLTP EHVFIHPGWK LLEVPEGRTN FDNDIALVRL KDPVKMGPTV SPICLPGTSS DYNLMDGDLG LISGWGRTEK RDRAVRLKAA RLPVAPLRKC KEVKVEKPTA DAEAYVFTPN MICAGGEKGM DSCKGDSGGA FAVQDPNDKT KFYAAGLVSW GPQCGTYGLY TRVKNYVDWI MKTMQENSTP RED

実験情報

• ビーム: 設備名称: PETRA III EMBL P12 / 地域: Hamburg / 国: Germany / 線源: X-ray synchrotron / 波長: 0.124 Å
• 検出器: 名称: Pilatus 2M

スキャン

タイトル: Inactivated complement factor 1 (C1) / 測定日: 2015年8月16日 / 保管温度: 20 °C / セル温度: 20 °C / 照射時間: 1 sec. / フレーム数: 100 / 単位: 1/nm /

	Min	Max
Q	0.0432	2.5309

距離分布関数 P(R)

ソフトウェア P(R): GNOM 5.0 / ポイント数: 243 /

	Min	Max
Q	0.0537556	0.693535
P(R) point	1	243
R	0	36.6

結果

Experimental MW: 790 kDa / カーブのタイプ: other
コメント: The expected MW quoted above (733 kDa) is calculated from the amino acid sequence of the oligomeric complex. The experimental MW of 790 kDa takes into account additional post-translational modifications of the protein. The models displayed in this entry - sequentially from top to bottom - represent those presented in Figure 4c of the main text and Supplementary Figures 2e and 4b, respectively, of Mortensen et al., 2017 Proc Natl Acad Sci U S A 114(5):986-991 .

	P(R)	P(R) error	Guinier	Guinier error
前方散乱 I0	49450	37	49602.1	80.17
慣性半径, Rg	11.46 nm	0.01	11.5 nm	0.1

	Min	Max
D	-	36.6
Guinier point	5	27