date: 2021-02-16T08:10:26Z
pdf:unmappedUnicodeCharsPerPage: 17
pdf:PDFVersion: 1.7
pdf:docinfo:title: Origin and Expansion of the Serine Protease Repertoire in the Myelomonocyte Lineage
xmp:CreatorTool: LaTeX with hyperref
Keywords: serine proteases; trypsin ancestor; complement factor D; proteinase 3; cleavage specificity
access_permission:modify_annotations: true
access_permission:can_print_degraded: true
subject: The deepest evolutionary branches of the trypsin/chymotrypsin family of serine proteases are represented by the digestive enzymes of the gastrointestinal tract and the multi-domain proteases of the blood coagulation and complement system. Similar to the very old digestive system, highly diverse cleavage specificities emerged in various cell lineages of the immune defense system during vertebrate evolution. The four neutrophil serine proteases (NSPs) expressed in the myelomonocyte lineage, neutrophil elastase, proteinase 3, cathepsin G, and neutrophil serine protease 4, collectively display a broad repertoire of (S1) specificities. The origin of NSPs can be traced back to a circulating liver-derived trypsin-like protease, the complement factor D ancestor, whose activity is tightly controlled by substrate-induced activation and TNF-induced locally upregulated protein secretion. However, the present-day descendants are produced and converted to mature enzymes in precursor cells of the bone marrow and are safely sequestered in granules of circulating neutrophils. The potential site and duration of action of these cell-associated serine proteases are tightly controlled by the recruitment and activation of neutrophils, by stimulus-dependent regulated secretion of the granules, and by various soluble inhibitors in plasma, interstitial fluids, and in the inflammatory exudate. An extraordinary dynamic range and acceleration of immediate defense responses have been achieved by exploiting the high structural plasticity of the trypsin fold.
dc:creator: Stefanie A. I. Weiss, Salome R. T. Rehm, Natascha C. Perera, Martin L. Biniossek, Oliver Schilling and Dieter E. Jenne
dcterms:created: 2021-02-16T08:02:55Z
Last-Modified: 2021-02-16T08:10:26Z
dcterms:modified: 2021-02-16T08:10:26Z
dc:format: application/pdf; version=1.7
title: Origin and Expansion of the Serine Protease Repertoire in the Myelomonocyte Lineage
Last-Save-Date: 2021-02-16T08:10:26Z
pdf:docinfo:creator_tool: LaTeX with hyperref
access_permission:fill_in_form: true
pdf:docinfo:keywords: serine proteases; trypsin ancestor; complement factor D; proteinase 3; cleavage specificity
pdf:docinfo:modified: 2021-02-16T08:10:26Z
meta:save-date: 2021-02-16T08:10:26Z
pdf:encrypted: false
dc:title: Origin and Expansion of the Serine Protease Repertoire in the Myelomonocyte Lineage
modified: 2021-02-16T08:10:26Z
cp:subject: The deepest evolutionary branches of the trypsin/chymotrypsin family of serine proteases are represented by the digestive enzymes of the gastrointestinal tract and the multi-domain proteases of the blood coagulation and complement system. Similar to the very old digestive system, highly diverse cleavage specificities emerged in various cell lineages of the immune defense system during vertebrate evolution. The four neutrophil serine proteases (NSPs) expressed in the myelomonocyte lineage, neutrophil elastase, proteinase 3, cathepsin G, and neutrophil serine protease 4, collectively display a broad repertoire of (S1) specificities. The origin of NSPs can be traced back to a circulating liver-derived trypsin-like protease, the complement factor D ancestor, whose activity is tightly controlled by substrate-induced activation and TNF-induced locally upregulated protein secretion. However, the present-day descendants are produced and converted to mature enzymes in precursor cells of the bone marrow and are safely sequestered in granules of circulating neutrophils. The potential site and duration of action of these cell-associated serine proteases are tightly controlled by the recruitment and activation of neutrophils, by stimulus-dependent regulated secretion of the granules, and by various soluble inhibitors in plasma, interstitial fluids, and in the inflammatory exudate. An extraordinary dynamic range and acceleration of immediate defense responses have been achieved by exploiting the high structural plasticity of the trypsin fold.
pdf:docinfo:subject: The deepest evolutionary branches of the trypsin/chymotrypsin family of serine proteases are represented by the digestive enzymes of the gastrointestinal tract and the multi-domain proteases of the blood coagulation and complement system. Similar to the very old digestive system, highly diverse cleavage specificities emerged in various cell lineages of the immune defense system during vertebrate evolution. The four neutrophil serine proteases (NSPs) expressed in the myelomonocyte lineage, neutrophil elastase, proteinase 3, cathepsin G, and neutrophil serine protease 4, collectively display a broad repertoire of (S1) specificities. The origin of NSPs can be traced back to a circulating liver-derived trypsin-like protease, the complement factor D ancestor, whose activity is tightly controlled by substrate-induced activation and TNF-induced locally upregulated protein secretion. However, the present-day descendants are produced and converted to mature enzymes in precursor cells of the bone marrow and are safely sequestered in granules of circulating neutrophils. The potential site and duration of action of these cell-associated serine proteases are tightly controlled by the recruitment and activation of neutrophils, by stimulus-dependent regulated secretion of the granules, and by various soluble inhibitors in plasma, interstitial fluids, and in the inflammatory exudate. An extraordinary dynamic range and acceleration of immediate defense responses have been achieved by exploiting the high structural plasticity of the trypsin fold.
Content-Type: application/pdf
pdf:docinfo:creator: Stefanie A. I. Weiss, Salome R. T. Rehm, Natascha C. Perera, Martin L. Biniossek, Oliver Schilling and Dieter E. Jenne
X-Parsed-By: org.apache.tika.parser.DefaultParser
creator: Stefanie A. I. Weiss, Salome R. T. Rehm, Natascha C. Perera, Martin L. Biniossek, Oliver Schilling and Dieter E. Jenne
meta:author: Stefanie A. I. Weiss, Salome R. T. Rehm, Natascha C. Perera, Martin L. Biniossek, Oliver Schilling and Dieter E. Jenne
dc:subject: serine proteases; trypsin ancestor; complement factor D; proteinase 3; cleavage specificity
meta:creation-date: 2021-02-16T08:02:55Z
created: 2021-02-16T08:02:55Z
access_permission:extract_for_accessibility: true
access_permission:assemble_document: true
xmpTPg:NPages: 20
Creation-Date: 2021-02-16T08:02:55Z
pdf:charsPerPage: 4094
access_permission:extract_content: true
access_permission:can_print: true
meta:keyword: serine proteases; trypsin ancestor; complement factor D; proteinase 3; cleavage specificity
Author: Stefanie A. I. Weiss, Salome R. T. Rehm, Natascha C. Perera, Martin L. Biniossek, Oliver Schilling and Dieter E. Jenne
producer: pdfTeX-1.40.21
access_permission:can_modify: true
pdf:docinfo:producer: pdfTeX-1.40.21
pdf:docinfo:created: 2021-02-16T08:02:55Z