BENZON SYMPOSIUM No. 50 The Lipocalin Protein Superfamily

August 24-28, 2003 – Copenhagen, Denmark

Organizing committee: Bo Åkerström (Lund), Darren Flower (Compton), Jean-Philippe Salier (Rouen) and Niels Borregaard (Copenhagen),

Invited speakers and chairmen: Russell E. BISHOP – Niels BORREGAARD – Christian H. CAMBILLAU – Frank CLAESSENS –Fiorella DESCALZI CANCEDDA – Jim van DIJK – Darren R. FLOWER – Ben GLASGOW – Yuji GOTO– Lennart LÖGDBERG – Henriette MOLINARI – Rauno MÄNTYJÄRVI – William R. MONTFORT – Marcia NEWCOMER – Guido PAESEN – Paolo PELOSI – Eric RASSART Bernhard REDL – Jean-Philippe SALIER – Diego SANCHEZ – Lindsay SAWYER Markku Seppälä – Arne SKERRA – Roland K. STRONG – Yoshihiro URADE – Bo ÅKERSTRÖM

Synopsis: The lipocalin protein superfamily is one of the most remarkable protein superfamilies exhibiting extraordinary diversity at the level of sequence and function. It consists of more than 25 small extracellular proteins originating from a wide variety of tissues in vertebrate and invertebrate animals, plants and bacteria. Lipocalins are characterised by three molecular recognition properties: the binding of small hydrophobic substances, the binding to cell-surface receptors, and the formation of complexes with other soluble macromolecules A typical lipocalin consists of a 160-180 amino-acid peptide, folded into 8-9 b-strands which form a coffee filter-like cone with a hydrophobic interior. The plasma proteins: retinol-binding protein, orosomucoid, and a1-microglobulin, the nasal odorant-binding proteins, the bilin-binding proteins of butterflies and crustacyanin, the protein which gives the shell of crayfish its unusual colour properties, are all examples of lipocalins.

Clinical studies have shown the importance of many lipocalins in health and disease: the plasma levels of a1-acid-glycoprotein- and neutrophil-gelatinase associated-lipocalin are significantly increased in acute, systemic inflammation in mammals; a1-microglobulin has become the major urinary marker of renal disorders; glycodelin is a biochemical marker in pregnancy. Lipocalins have been implicated at one stage or another of pathophysiogical events such as acute systemic inflammation (the anti-Tumor Necrosis Factor activity of a1-acid-glycoprotein), nerve growth (lazarillo) and regeneration (apolipoprotein D), the proliferation of cancer cells (apolipoprotein D; neutrophil gelatinase-associated lipocalin) or allergy (the allergenic power of a cockroach lipocalin). Recent research has shown that, in the future, new recombinant lipocalins may, in the future, be of use as laboratory reagents analogous to antibodies.

The lipocalin protein superfamily was defined fifteen years ago. Since then, our knowledge of the proteins has expanded enormously. One or more new lipocalins are discovered every year. Benzon Symposium No. 50 will be devoted to this subject. Sessions will focus on structural principles, evolutionary relationships, similarities and differences in gene organization, clinical aspects as well as structure and functions of individual lipocalins.

Clinical studies have shown the importance of many lipocalins in health and disease: the plasma levels of a1-acid-glycoprotein and neutrophil-gelatinase associated lipocalin are significantly increased in acute, systemic inflammation in mammals; a1-microglobulin has become the major urinary marker of renal disorders; glycodelin is a biochemical marker in pregnancy. Lipocalins have been implicated at one stage or another of physiopathological events such as acute systemic inflammation (e.g. the anti-Tumor Necrosis Factor activity of a1-acid-glycoprotein), nerve growth (lazarillo) and regeneration (e.g.: apolipoprotein D), the proliferation of cancer cells (e.g.: apolipoprotein D; neutrophil gelatinase-associated lipocalin) or allergy (e.g. the allergenic power of a coackroach lipocalin). Recent research has shown that new recombinant lipocalins may, in the future, be of use as laboratory reagents analogous to antibodies.

The lipocalin protein superfamily was defined fifteen years ago. Since then, our knowledge of the proteins has expanded enormously. One or more new lipocalins are discovered every year. The Benzon Symposium no. 50 will be devoted to this subject. Sessions will be devoted to structural principles, evolutionary relationships, similarities and differences in gene organization, clinical aspects as well as structure and functions of individual lipocalins.

Scientific Programme:
Niels Borregaard: Introduction

Session I: Lipocalin genes and evolution of lipocalins
Chairmen: Frank Claessens & Paolo Pelosi
Russell E. BISHOP: Structural Relationships Between Bacterial Lipocalins and Outer Membrane Beta-barrel Proteins
Bernard REDL: Tear Lipocalin Genes – Structures and Regulatory Elements
Jean-Philippe SALIER: Chromosomal Location and Organization of Lipocalin Genes
Diego SANCHEZ: Molecular Evolution of the Lipocalin Family
Jean-Benoit F. CHARRON: Cold-regulated Plant Lipocalins (Poster No. I-1)
Aldo PAGANO: The Chondrogenesis Associated Lipocalins (Poster No. I-2)
Kichiya SUZUKI: Identification of a Cluster of Epididymal Lipocalins on the Murine Chromosome 2 [A3] Region (Poster No. I-3)
Jack COWLAND: Neutrophil Gelatinase-Associated (NGAL) is Upregulated in Human Epithelial Cells by IL-1ß but not by TNF-a (Poster No. I-4)

Session II: Structure and function of individual lipocalins 1
Chairmen: Jean-Philippe Salier & Diego Sanchez
Bo ÅKERSTRÖM: Heme- and Radical Savenger Properties of a1-Microglobulin
Ben GLASGOW: The Structure and Function of Tear Lipocalin v

Session II: Structure and function of individual lipocalins 2
Chairmen: Marcia Newcomer & Arne Skerra
William R. MONTFORT: Nitric Oxide Transport by Lipocalins from Blood-sucking Insects
Eric RASSART: Apolipoprotein D
Guido PAESEN: Structure and Function of Histamine-binding Proteins and Related Lipocalins from Ticks
Paolo PELOSI: Structure and Function of Odorant-binding Protein
Ulla-Maja BAILEY: The Drosophila Lipocalin, Karl, Is Specifically Expressed in the Blood Cell Compartment (Poster No. II-1)
María D. GANFORNIA: Genetic Analysis of the Lipocalin Lazarillo Function: A Multiorganismal Approach (Poster No. II-2)
M. NILSEN-HAMILTON: Uterocalin/24p3, An Acute Phase Protein Expressed by the Mammary Gland (Poster No. II-3)
Maria ALLHORN: The Lipocalin a1-Microglobulin Generates Superoxide Radicals (Poster No. II-4)
Lindsay SAWYER: ß-Lactoglobulin – Structure, Properties and Function
Roland K. STRONG: Siderocalin, Siderophores and Iron

Session III: Structure of lipocalins
Chairmen: Darren Flower & Roland K. Strong
Christian H. CAMBILLAU: Crystal Structures of Pheromones and Odor Transport Lipocalins
Marcia NEWCOMER: Retinol Binding Protein: Structure and Function
Yuji GOTO: Conformation and Folding of Bovine ß-Lactoglobulin
Henriette MOLINARI: Folding and Interaction Studies of ß-Lactoglobulins and Liver Basic Fatty Acid Binding Protein
Yoshihiro URADE: Functional and Structural Analyses of Lipocalin-type Prostaglandin D Synthase (Beta-Trace) (Poster No. III-1)
Lesley GREENE: Nature of Sequence and Structural Conservation in the Lipocalin Superfamily: Relationship to Folding and Stability (Poster No. III-2)
Pierre J. RIZKALLAH: The Molecular Basis of the Coloration Mechanism in Lobster Shell: Beta-crustacyanin at 3.2 Å Resolution (Poster No. III-3)
James M. SODETZ: Human Complement Protein C8g: The Sole Lipocalin in the Complement System (Poster No. III-4)

Session IV: Lipocalins in disease and medicine 1
Chairmen: Lennart Lögdberg & Anders Grubb
Niels BORREGAARD: Neutrophil Gelatinase-Associated Lipocalin in Health and Disease
Rauno MÄNTYJÄRVI: Lipocalin Allergens

Session IV: Lipocalins in disease and medicine 2
Chairmen: Bo Åkerström & Rauno Mäntyjärvi
W. van DIJK: Anti-inflammatory Properties of Specific Glycoforms of a1-Acid Glycoprotein
Lennart LÖGDBERG: An Update on the Immunocalins, the Immunomodulatory Lipocalins
Fiorella Descalzi CANCEDDA: EX-FABP in Differentiation and Pathology
Markku SEPPÄLÄ: Glycodelin: A major Lipocalin Protein of the Reproductive Axis With Diverse Actions in Gamete Binding, Immune Reactions and Differentiation
Anjali KARANDE: Glycodelin A: An Immunocalin with Apoptotic Activity (Poster No. II-5)
Gilbert HAUG: Construction of Anticalins as Antagonistic Agents for the Target-specific Intervention In Autoimmune Diseases (Poster No. IV-2)
Mark L. TYKOCINSKI: Unique T Cell Immunoregulatory Properties of the Lipocalin Placental Protein 14 (Poster No. IV-3)
María V. CROCE: a1-Acid Gglycoprotein (AAG), A Possible Carrier of Sialyl Lewis X (SLEWIS X) Antigen In Colorectal Carcinoma (Poster No. IV-4)
Session V: Future of lipocalin research
Chairmen: Yoshihiro Urade & Lindsay Sawyer
Arne SKERRA: Anticalins: Engineered Lipocalins With Antibody-like Ligand-binding Properties
Darren R. FLOWER: Lipocalin Research Beyond the Superfamilies: Future Horizons

Abstracts (pdf)