Vitronectin

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Vitronectin
The SMB domain (yellow) in complex with PAI-1
Available structures:
For the file format that describes the 3D structures of molecules found in the Protein Data Bank, see Protein Data Bank (file format).

The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free.

History

Founded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB).

The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community.

The PDB is a key resource in structural biology and is critical to more recent work in structural genomics.

Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution.

Growth

When the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off.

The growth rate of the PDB has been the subject of fairly extensive analysis.

Contents

As of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose.

Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used.

Statistics

As of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:

Proteins Nucleic Acids Protein/NA complexes Other Total
X-ray diffraction 36223 983 1684 24 38914
NMR 5665 781 134 7 6587
Electron microscopy 105 10 38 0 153
Other 80 4 4 2 90
Total 42073 1778 1860 33 45744

Note that theoretical models are no longer accepted in the PDB.

22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file.

The current breakdown of holdings is updated weekly.

File format

Through the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.

This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects;

The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons.

Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs.

If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction).

Various funding agencies and scientific journals now require scientists to submit their structure data to PDB.

Viewing the data

The structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software.

References

Printed

  • H.M. Berman, K. Henrick, H. Nakamura (2003): Announcing the worldwide Protein Data Bank. Nature Structural Biology 10 (12), p. 980 PMID 14634627.
  • H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne: The Protein Data Bank. Nucleic Acids Research, 28 pp. 235-242 (2000). PMID 10592235
  • Bernstein FC, Koetzle TF, Williams GJ, Meyer Jr EF, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol 1977;112:535-542. PMID 875032.
  • E.F. Meyer “The First Years of the Protein Data Bank“, Protein Science 6:1591-1597 (1997)
  • Sussman, JL, Lin, D, Jiang, J, Manning, NO, Prilusky, J, Ritter, O & Abola, EE. Protein data bank (PDB): a database of 3D structural information of biological macromolecules. Acta Cryst 1998; D54:1078-1084. PMID 10089483.

Online

Other external links

Links to enzyme database data

  • [1] The best mapping is provided by Kim Henrick's group at EBI as part of the MSD SIFTS initiative.
  • [2] PDB provide a mapping on their beta site, but it is at the whole PDB level not chain level.
  • [3] Search at BRENDA enzyme database portal.
  • [4] PDBSProtEC:

Molecular graphic visualisation tools

The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free.

History

Founded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB).

The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community.

The PDB is a key resource in structural biology and is critical to more recent work in structural genomics.

Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution.

Growth

When the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off.

The growth rate of the PDB has been the subject of fairly extensive analysis.

Contents

As of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose.

Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used.

Statistics

As of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:

Proteins Nucleic Acids Protein/NA complexes Other Total
X-ray diffraction 36223 983 1684 24 38914
NMR 5665 781 134 7 6587
Electron microscopy 105 10 38 0 153
Other 80 4 4 2 90
Total 42073 1778 1860 33 45744

Note that theoretical models are no longer accepted in the PDB.

22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file.

The current breakdown of holdings is updated weekly.

File format

Through the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.

This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects;

The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons.

Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs.

If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction).

Various funding agencies and scientific journals now require scientists to submit their structure data to PDB.

Viewing the data

The structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software.

References

Printed

  • H.M. Berman, K. Henrick, H. Nakamura (2003): Announcing the worldwide Protein Data Bank. Nature Structural Biology 10 (12), p. 980 PMID 14634627.
  • H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne: The Protein Data Bank. Nucleic Acids Research, 28 pp. 235-242 (2000). PMID 10592235
  • Bernstein FC, Koetzle TF, Williams GJ, Meyer Jr EF, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol 1977;112:535-542. PMID 875032.
  • E.F. Meyer “The First Years of the Protein Data Bank“, Protein Science 6:1591-1597 (1997)
  • Sussman, JL, Lin, D, Jiang, J, Manning, NO, Prilusky, J, Ritter, O & Abola, EE. Protein data bank (PDB): a database of 3D structural information of biological macromolecules. Acta Cryst 1998; D54:1078-1084. PMID 10089483.

Online

Other external links

Links to enzyme database data

  • [5] The best mapping is provided by Kim Henrick's group at EBI as part of the MSD SIFTS initiative.
  • [6] PDB provide a mapping on their beta site, but it is at the whole PDB level not chain level.
  • [7] Search at BRENDA enzyme database portal.
  • [8] PDBSProtEC:

Molecular graphic visualisation tools

The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free.

History

Founded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB).

The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community.

The PDB is a key resource in structural biology and is critical to more recent work in structural genomics.

Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution.

Growth

When the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off.

The growth rate of the PDB has been the subject of fairly extensive analysis.

Contents

As of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose.

Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used.

Statistics

As of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:

Proteins Nucleic Acids Protein/NA complexes Other Total
X-ray diffraction 36223 983 1684 24 38914
NMR 5665 781 134 7 6587
Electron microscopy 105 10 38 0 153
Other 80 4 4 2 90
Total 42073 1778 1860 33 45744

Note that theoretical models are no longer accepted in the PDB.

22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file.

The current breakdown of holdings is updated weekly.

File format

Through the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.

This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects;

The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons.

Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs.

If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction).

Various funding agencies and scientific journals now require scientists to submit their structure data to PDB.

Viewing the data

The structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software.

References

Printed

  • H.M. Berman, K. Henrick, H. Nakamura (2003): Announcing the worldwide Protein Data Bank. Nature Structural Biology 10 (12), p. 980 PMID 14634627.
  • H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne: The Protein Data Bank. Nucleic Acids Research, 28 pp. 235-242 (2000). PMID 10592235
  • Bernstein FC, Koetzle TF, Williams GJ, Meyer Jr EF, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol 1977;112:535-542. PMID 875032.
  • E.F. Meyer “The First Years of the Protein Data Bank“, Protein Science 6:1591-1597 (1997)
  • Sussman, JL, Lin, D, Jiang, J, Manning, NO, Prilusky, J, Ritter, O & Abola, EE. Protein data bank (PDB): a database of 3D structural information of biological macromolecules. Acta Cryst 1998; D54:1078-1084. PMID 10089483.

Online

Other external links

Links to enzyme database data

  • [9] The best mapping is provided by Kim Henrick's group at EBI as part of the MSD SIFTS initiative.
  • [10] PDB provide a mapping on their beta site, but it is at the whole PDB level not chain level.
  • [11] Search at BRENDA enzyme database portal.
  • [12] PDBSProtEC:

Molecular graphic visualisation tools

Identifiers
Symbol(s) VTN; V75; VN; VNT
External IDs OMIM: 193190 MGI: 98940 Homologene: 532
RNA expression pattern

Image:PBB GE VTN 204534 at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 7448 22370
Ensembl ENSG00000109072 ENSMUSG00000017344
Uniprot P04004 Q5SYG4
Refseq NM_000638 (mRNA)
NP_000629 (protein) 		NM_011707 (mRNA)
NP_035837 (protein)
Location Chr 17: 23.72 - 23.72 Mb Chr 11: 78.32 - 78.32 Mb
Pubmed search [13] [14]

Vitronectin is an abundant glycoprotein found in blood plasma and the extracellular matrix. Vitronectin has been speculated to be involved in hemostasis and tumor malignancy.

Structure

Vitronectin is a 75 kDa glycoprotein, consisting of 459 amino acid residues. About one third of the proteins molecular mass is composed of carbohydrates. Occasionally the protein is cleaved after arginine 379, to produce two chain vitronectin, where the two parts are linked by a disulfide bond. No high resolution structure has been determined experimentally yet.

The protein consists of three domains:

Several structures has been reported for the Somatomedin B domain. Initially the protein was crystallized in complex with one of its physiological binding partners: the Plasminogen activator inhibitor-1 (PAI-1), and the structure solved for this complex[15]. Subsequently two groups reported NMR structures of the domain[16][17]. The Somatomedin B domain is a close knit disulfide knot, with 4 disulfide bonds within 35 residues. Different disulfide configurations had been reported for this domain[18][19][20] but this ambiguity has been resolved by the crystal structure[21].

Homology models have been built for the central and C-terminal domains[22].

Biology

The Somatomedin B domain of Vitronectin binds to Plasminogen activator inhibitor-1 (PAI-1), and stabilizes it. Thus vitronectin serves to regulate proteolysis initiated by plasminogen activation. Additionally vitronectin is a component of platelets and is thus involved in hemostasis. Vitronectin contains an RGD (45-47) sequence which is a binding site for membrane bound integrins, e.g. the vitronectin receptor, which serve to anchor cells to the extra cellular matrix. The Somatomedin B domain interacts with the urokinase receptor, and this interaction has been implicated in cell migration and signal transduction. High plasma levels of both PAI-1 and the urokinase receptor have been shown to correlate with a negative prognosis for cancer patients. Cell adhesion and migration are directly involved in cancer metastasis, which provides a probable mechanistic explanation for this observation.

References

  1. ^  Zhou A, Huntington JA, Pannu NS, Carrell RW, Read RJ (2003) How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration Nat Struct Biol. 2003 Jul;10(7):541-4 (full text article online: Entrez PubMed 12808446).
  2. ^  Kamikubo Y, De Guzman R, Kroon G, Curriden S, Neels JG, Churchill MJ, Dawson P, Oldziej S, Jagielska A, Scheraga HA, Loskutoff DJ, Dyson HJ. (2004) Disulfide bonding arrangements in active forms of the somatomedin B domain of human vitronectin. Biochemistry. 2004 Jun 1;43(21):6519-34 (full text article online: Entrez PubMed 15157085).
  3. ^  Mayasundari A, Whittemore NA, Serpersu EH, Peterson CB. (2004) The solution structure of the N-terminal domain of human vitronectin: proximal sites that regulate fibrinolysis and cell migration. J Biol Chem. 2004 Jul 9;279(28):29359-66. Epub 2004 Apr 30 (full text article online: Entrez PubMed 15123712).
  4. ^  Kamikubo Y, Okumura Y, Loskutoff DJ. (2002) Identification of the disulfide bonds in the recombinant somatomedin B domain of human vitronectin. J Biol Chem. 2002 Jul 26;277(30):27109-19. Epub 2002 May 17 (full text article online: Entrez PubMed 12019263).
  5. ^  Horn NA, Hurst GB, Mayasundari A, Whittemore NA, Serpersu EH, Peterson CB.(2004) Assignment of the four disulfides in the N-terminal somatomedin B domain of native vitronectin isolated from human plasma. J Biol Chem. 2004 Aug 20;279(34):35867-78. Epub 2004 Jun 1. (full text article online: Entrez PubMed 15173163).
  6. ^  Xu D, Baburaj K, Peterson CB, Xu Y (2001) Model for the three-dimensional structure of vitronectin: predictions for the multi-domain protein from threading and docking Proteins. 2001 Aug 15;44(3):312-20 (full text article online: Entrez PubMed 11455604).
  7. ^  Zhou A, Huntington JA, Pannu NS, Carrell RW, Read RJ (2003) How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration Nat Struct Biol. 2003 Jul;10(7):541-4 (full text article online: Entrez PubMed 12808446).
  8. ^  Xu D, Baburaj K, Peterson CB, Xu Y (2001) Model for the three-dimensional structure of vitronectin: predictions for the multi-domain protein from threading and docking Proteins. 2001 Aug 15;44(3):312-20 (full text article online: Entrez PubMed 11455604).

External links

v • d • e
Protein: glycoproteins
Activin - ADAM protein - Alpha 1-antichymotrypsin - Apolipoprotein H - CD70 - Asialoglycoprotein - Avidin - B-cell activating factor - 4-1BB ligand - Cholesterylester transfer protein - Clusterin - Colony-stimulating factor - Haemopexin - Inhibin - Lactoferrin - Membrane glycoproteins - Mucoprotein - Myelin protein zero - Osteonectin - Protein C - Protein S - Proteoglycan - Serum Amyloid P component - Sialoglycoprotein (CD43, Glycophorin, Glycophorin C) - Thrombopoietin - Thyroglobulin - Thyroxine-binding proteins - Transcortin - Tumor necrosis factor-alpha - Uteroglobin - Vitronectin


Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .

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