8os5

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the Factor XII heavy chain reveals an interlocking dimer with a FnII to kringle domain interaction

Structural highlights

8os5 is a 3 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 3.4Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FA12_HUMAN Congenital factor XII deficiency;Hereditary angioedema type 3. Defects in F12 are the cause of factor XII deficiency (FA12D) [MIM:234000; also known as Hageman factor deficiency. This trait is an asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. F12 deficiency is divided into two categories, a cross-reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] Defects in F12 are the cause of hereditary angioedema type 3 (HAE3) [MIM:610618; also known as estrogen-related HAE or hereditary angioneurotic edema with normal C1 inhibitor concentration and function. HAE is characterized by episodic local subcutaneous edema, and submucosal edema involving the upper respiratory and gastrointestinal tracts. HAE3 occurs exclusively in women and is precipitated or worsened by high estrogen levels (e.g. during pregnancy or treatment with oral contraceptives). It differs from HAE types 1 and 2 in that both concentration and function of C1 inhibitor are normal.^[10] ^[11]

Function

FA12_HUMAN Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa.^[12]

Publication Abstract from PubMed

The contact system is composed of Factor XII (FXII), prekallikrein (PK) and co-factor kininogen (HK). The globular C1q receptor (gC1qR) has been shown to interact with FXII and HK. We reveal the FXII fibronectin type II domain (FnII) binds gC1qR in a Zn2+ dependent fashion and determined the complex crystal structure. FXIIFnII binds the gC1qR trimer in an asymmetric fashion with residues Arg36 and Arg65 forming contacts with two distinct negatively charged pockets. gC1qR residues Asp185 and His187 coordinate a Zn2+ adjacent to the FXII binding site and a comparison with the ligand free gC1qR crystal structure reveals the anionic G1-loop becomes ordered upon FXIIFnII binding. Additional conformational changes in the region of the Zn2+ binding site reveal an allosteric basis for Zn2+ modulation of FXII binding. Mutagenesis coupled with SPR demonstrate the gC1qR Zn2+ site contributes to FXII binding and plasma based assays reveal gC1qR stimulates coagulation in a FXII-dependent manner. Analysis of the binding of HK domain 5 (HKD5) to gC1qR shows only one high affinity binding site per trimer. Mutagenesis studies identify a critical G3-loop located at the center of the gC1qR trimer suggesting steric occlusion as the mechanism for HKD5 asymmetric binding. Gel filtration experiments reveal that gC1qR clusters FXII and HK into a higher order 500kDa ternary complex. These results support the conclusion that extracellular gC1qR can act as a chaperone to cluster contact factors which may be a prelude for initiating the cascades which drive bradykinin generation and the intrinsic pathway of coagulation.

Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery.,Kaira BG, Slater A, McCrae KR, Dreveny I, Sumya UM, Mutch NJ, Searle M, Emsley J Blood. 2020 Jun 19. pii: 461064. doi: 10.1182/blood.2020004818. PMID:32559765^[13]

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

References

↑ Schloesser M, Hofferbert S, Bartz U, Lutze G, Lammle B, Engel W. The novel acceptor splice site mutation 11396(G-->A) in the factor XII gene causes a truncated transcript in cross-reacting material negative patients. Hum Mol Genet. 1995 Jul;4(7):1235-7. PMID:8528215
↑ Bernardi F, Marchetti G, Patracchini P, del Senno L, Tripodi M, Fantoni A, Bartolai S, Vannini F, Felloni L, Rossi L, et al.. Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme. Blood. 1987 May;69(5):1421-4. PMID:2882793
↑ Miyata T, Kawabata S, Iwanaga S, Takahashi I, Alving B, Saito H. Coagulation factor XII (Hageman factor) Washington D.C.: inactive factor XIIa results from Cys-571----Ser substitution. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8319-22. PMID:2510163
↑ Hovinga JK, Schaller J, Stricker H, Wuillemin WA, Furlan M, Lammle B. Coagulation factor XII Locarno: the functional defect is caused by the amino acid substitution Arg 353-->Pro leading to loss of a kallikrein cleavage site. Blood. 1994 Aug 15;84(4):1173-81. PMID:8049433
↑ Schloesser M, Zeerleder S, Lutze G, Halbmayer WM, Hofferbert S, Hinney B, Koestering H, Lammle B, Pindur G, Thies K, Kohler M, Engel W. Mutations in the human factor XII gene. Blood. 1997 Nov 15;90(10):3967-77. PMID:9354665
↑ Kondo S, Tokunaga F, Kawano S, Oono Y, Kumagai S, Koide T. Factor XII Tenri, a novel cross-reacting material negative factor XII deficiency, occurs through a proteasome-mediated degradation. Blood. 1999 Jun 15;93(12):4300-8. PMID:10361128
↑ Kanaji T, Kanaji S, Osaki K, Kuroiwa M, Sakaguchi M, Mihara K, Niho Y, Okamura T. Identification and characterization of two novel mutations (Q421 K and R123P) in congenital factor XII deficiency. Thromb Haemost. 2001 Dec;86(6):1409-15. PMID:11776307
↑ Ishii K, Oguchi S, Moriki T, Yatabe Y, Takeshita E, Murata M, Ikeda Y, Watanabe K. Genetic analyses and expression studies identified a novel mutation (W486C) as a molecular basis of congenital coagulation factor XII deficiency. Blood Coagul Fibrinolysis. 2004 Jul;15(5):367-73. PMID:15205584
↑ Oguchi S, Ishii K, Moriki T, Takeshita E, Murata M, Ikeda Y, Watanabe K. Factor XII Shizuoka, a novel mutation (Ala392Thr) identified and characterized in a patient with congenital coagulation factor XII deficiency. Thromb Res. 2005;115(3):191-7. PMID:15617741 doi:10.1016/j.thromres.2004.08.027
↑ Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun. 2006 May 19;343(4):1286-9. PMID:16638441 doi:S0006-291X(06)00611-5
↑ Cichon S, Martin L, Hennies HC, Muller F, Van Driessche K, Karpushova A, Stevens W, Colombo R, Renne T, Drouet C, Bork K, Nothen MM. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III. Am J Hum Genet. 2006 Dec;79(6):1098-104. Epub 2006 Oct 18. PMID:17186468 doi:S0002-9297(07)63472-7
↑ MacQuarrie JL, Stafford AR, Yau JW, Leslie BA, Vu TT, Fredenburgh JC, Weitz JI. Histidine-rich glycoprotein binds factor XIIa with high affinity and inhibits contact-initiated coagulation. Blood. 2011 Apr 14;117(15):4134-41. doi: 10.1182/blood-2010-07-290551. Epub 2011 , Feb 8. PMID:21304106 doi:10.1182/blood-2010-07-290551
↑ Kaira BG, Slater A, McCrae KR, Dreveny I, Sumya U, Mutch NJ, Searle M, Emsley J. Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery. Blood. 2020 Oct 1;136(14):1685-1697. PMID:32559765 doi:10.1182/blood.2020004818

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8os5"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8os5 is ON HOLD
+==Crystal structure of the Factor XII heavy chain reveals an interlocking dimer with a FnII to kringle domain interaction==
+<StructureSection load='8os5' size='340' side='right'caption='[[8os5]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8os5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OS5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OS5 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8os5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8os5 OCA], [https://pdbe.org/8os5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8os5 RCSB], [https://www.ebi.ac.uk/pdbsum/8os5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8os5 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/FA12_HUMAN FA12_HUMAN] Congenital factor XII deficiency;Hereditary angioedema type 3. Defects in F12 are the cause of factor XII deficiency (FA12D) [MIM:[https://omim.org/entry/234000 234000]; also known as Hageman factor deficiency. This trait is an asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. F12 deficiency is divided into two categories, a cross-reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection).<ref>PMID:8528215</ref> <ref>PMID:2882793</ref> <ref>PMID:2510163</ref> <ref>PMID:8049433</ref> <ref>PMID:9354665</ref> <ref>PMID:10361128</ref> <ref>PMID:11776307</ref> <ref>PMID:15205584</ref> <ref>PMID:15617741</ref>   Defects in F12 are the cause of hereditary angioedema type 3 (HAE3) [MIM:[https://omim.org/entry/610618 610618]; also known as estrogen-related HAE or hereditary angioneurotic edema with normal C1 inhibitor concentration and function. HAE is characterized by episodic local subcutaneous edema, and submucosal edema involving the upper respiratory and gastrointestinal tracts. HAE3 occurs exclusively in women and is precipitated or worsened by high estrogen levels (e.g. during pregnancy or treatment with oral contraceptives). It differs from HAE types 1 and 2 in that both concentration and function of C1 inhibitor are normal.<ref>PMID:16638441</ref> <ref>PMID:17186468</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/FA12_HUMAN FA12_HUMAN] Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa.<ref>PMID:21304106</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The contact system is composed of Factor XII (FXII), prekallikrein (PK) and co-factor kininogen (HK). The globular C1q receptor (gC1qR) has been shown to interact with FXII and HK. We reveal the FXII fibronectin type II domain (FnII) binds gC1qR in a Zn2+ dependent fashion and determined the complex crystal structure. FXIIFnII binds the gC1qR trimer in an asymmetric fashion with residues Arg36 and Arg65 forming contacts with two distinct negatively charged pockets. gC1qR residues Asp185 and His187 coordinate a Zn2+ adjacent to the FXII binding site and a comparison with the ligand free gC1qR crystal structure reveals the anionic G1-loop becomes ordered upon FXIIFnII binding. Additional conformational changes in the region of the Zn2+ binding site reveal an allosteric basis for Zn2+ modulation of FXII binding. Mutagenesis coupled with SPR demonstrate the gC1qR Zn2+ site contributes to FXII binding and plasma based assays reveal gC1qR stimulates coagulation in a FXII-dependent manner. Analysis of the binding of HK domain 5 (HKD5) to gC1qR shows only one high affinity binding site per trimer. Mutagenesis studies identify a critical G3-loop located at the center of the gC1qR trimer suggesting steric occlusion as the mechanism for HKD5 asymmetric binding. Gel filtration experiments reveal that gC1qR clusters FXII and HK into a higher order 500kDa ternary complex. These results support the conclusion that extracellular gC1qR can act as a chaperone to cluster contact factors which may be a prelude for initiating the cascades which drive bradykinin generation and the intrinsic pathway of coagulation.
-Authors:
+Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery.,Kaira BG, Slater A, McCrae KR, Dreveny I, Sumya UM, Mutch NJ, Searle M, Emsley J Blood. 2020 Jun 19. pii: 461064. doi: 10.1182/blood.2020004818. PMID:32559765<ref>PMID:32559765</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8os5" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Brown A]]
+[[Category: Emsley J]]
+[[Category: Kaira BG]]
+[[Category: Li C]]
+[[Category: Philippou H]]
+[[Category: Saleem M]]
+[[Category: Wilson C]]

8os5

From Proteopedia

Current revision

Crystal structure of the Factor XII heavy chain reveals an interlocking dimer with a FnII to kringle domain interaction

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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