Lectin Biochemistry

Lectins

These are specialized proteins that bind specific carbohydrates on cell surfaces

1 < 2

QC: Source of lectins (1) Animal (2) Plant source

F - Contains 2 or more sugar binding sites
F - Oligomeric
T
F - Recognize both N- and O- Glycans

T/F: Structure of a lectin

1.) Contains 1 sugar binding site
2.) Is a monomer
3.) High stereospecificity for glycans
4.) Recognize N- but not O- glycans

Multivalent

This characteristic of lectins describes their low single-site affinity which is attributed to their multiple carbohydrate binding sites

Intracellular CRDs

This kind of lectin is found in luminal compartments and function to sort, traffic, and target glycoproteins on cell surfaces

Extracellular CRDs

This kind of lectin is found external to the cell and is either secreted to bound to the plasma membrane

Carbohydrate-Recognition Domains

These are the sugar binding sites of lectins

Precipitation with 30-60% Ammonium Sulfate

In the laboratory, lectins can be demonstrated by what substance via what chemical reaction?

Ruthenium Red

This staining method reveals the carbohydrate-rich domains on plasma membranes

T

T/F: Lectins form weak interactions with carbohydrates to ensure specificity while being able to unlink as necessary

F

T/F: Each lectin-CHO interaction is strong but becomes weaker as they work together 

Face-to-face

This mechanism of lectin-carbohydrate interaction is described as the simultaneous binding of 2 or more CRDs with 2 different sites on the same carbohydrate molecule

Bind-and-slide

This mechanism of lectin-carbohydrate interaction is described as the binding of one site at a time along the carbohydrate molecule

Cross linking

This mechanism of lectin-carbohydrate interaction is described as the binding of the same lectin molecule to 2 carbohydrate units at the same time

Cell-to-cell contact and transient cell-to-cell adhesion

Function of lectins in animals

Sperm-Egg interactions, Blood Clotting, Lymphocyte Recirculation, Inflammatory responses

4 transient cell-to-cell adhesion functions of lectins in animals

Defense mechanism against insects, microorganisms, and pests

Function of lectins in plants

Allow them to adhere to epithelial cells of the GI tract by recognizing oligosaccharide units

Function of lectins in bacteria

1 < 2

QC: Lectin concentration required for agglutination to occur in (1) Malignant (2) Normal Cells

Amino acid sequences and Biochemical properties

2 basis of lectin classification

C-type, S-type, Eglectins, Ficolins, Pentraxins

5 families of lectins with known protein sequence homologies

Annexins, Amphoterin, Tachylectin, Complement Factor H

4 families of lectins with unknown protein sequence homologies

C-type

These are calcium requiring lectins found in animals

Calcium

This bridges the protein and sugar hydroxyl groups of C-type lectins via direct interactions

Glutamate

Amino acid residues that are found in C-type lectins

CRD variation due to amino acid sequence

What creates the differences in carbohydrate binding specificity in C-type lectin?

Collectins

This is the soluble type of C-type lectin

Selectins

This is the transmembrane type of C-type lectin

F - Bound via Disulfide Bridges

T

T

F - Cysteine-rich region

MTF: Structure of collectins

1.) Have 3 identical polypeptide chains bound to the N-terminal via hydrogen bonds

2.) Has an N-terminal domain with Gly-X-Y triple helix

3.) Is an oligomer

4.) The identical polypeptide chains have a short N-terminal glutamate-rich region

F - It’s on the N-terminal

T

F - Has only 1 EGF domain

F - Attached by GAGs

MTF: Structure of selectins

1.) Has a single-type lectin domain on the C-terminal

2.) Has a transmembrane domain on the C-terminal

3.) Has 2 EGF domains

4.) Has 2 complementary domains attached by glycoproteins

L-selectins

This form of selectin is found on the lymph node vessels and are expressed on the lymphocytic surfaces

E-selectins

This form of selectin is expressed on endothelial cells and bind to carbohydrates of cells crossing by

P-selectins

This form of selectin is expressed on endothelial cells and recognize oligosaccharides on polymorphonuclear cells (neutrophils) during inflammation

Galectin

These are cytoplasmic lectins that bind to galactose and its derivatives to function for cell development and differentiation

T
F - No sugar chains
T
F - At the N-terminal
T

MTF: Structure of galectin

1.) No disulfide bonds
2.) Has sugar chains
3.) No signal sequences
4.) N-acetylated at the C-Terminal
5.) Require metal for binding galactose

Proto

This type of galectin has 2 identical CRDs that crosslink homologous carbohydrate ligands

Chimera

This type of galectin has a non-lectin and galectin CRD that crosslink non-carbohydrate and carbohydrate ligands

Tandem-repeat

This type of galectin has 2 distinct CRDs that crosslink different carbohydrate ligands

Galectin-1,2,5,7,10

Galectins that are classified as proto

Galectin-3

Galectins that are classified as chimera

Galectin-4,6,8,9

Galectins that are classified as tandem-repeat

Eglectins

These are N-glycosylated lectins that bind galactosyl terminal glycans in frog egg jelly

T

T/F: Eglectins require Ca2+ to function

Intelectins

Term used to describe eglectins in humans

Block polyspermy in eggs, Stimulate Phagocytosis, Assist in adhesion, and serve a receptor function

Functions of eglectin

Ficolins

This is a soluble mammalian lectin that recognize unique sugar patterns on microbes

F

T/F: Ficolins require Ca2+ to function

F; It provides dimension and flexibility

T/F: Ficolins have domains clustered at the end of a triple helix collagen fiber that provides rigidity

Opsonins that present microbes to phagocytes

Direct function of ficolins

Opsonization with complement proteins

Indirect function of ficolins

Body fluids and at the interface with the environment

Location of ficolins

Pentraxins

This is the oldest known type of lectins and is established in host defense and survival

Ring of 5 identical polypeptide subunits

Describe the structure of pentraxins

T

T/F: Pentraxins are acute phase proteins that require calcium to function

Phosphorylcholine

Human C Reactive Protein has a high affinity of what phospholipid

Human C Reactive Protein

This pentraxin is used as an inflammatory marker

Galactans and Galactose Phosphate

Human C Reactive Protein binds what two substances?

Serum Amyloid P Component

This pentraxins significantly forms tissue deposits in amyloidosis

Annexins

This lectin acts as receptors for extracellular proteins, regulates phospholipase A2 activity, and is involved in endocytosis, exocytosis, vesicular transport, and trafficking

F; inner leaflet

T/F: Annexins preferably bind phospholipids at the outer leaflet of the membrane bilayer

Phosphatidylethanolamine, Phosphatidylserine, Phosphatidylinositol

3 phospholipids that annexins bind

F; Carbonyl terminal

T/F: Annexins contain binding sites at the amino terminal for calcium and phospholipid binding

T

T/F: Annexins are capable of relocating from the cytosol to the extracellular side

Sialic Acid

Viruses bind to CHO receptors on host cells by recognizing what substance on cell surfaces

Hemagglutinin

Viral protein that allows the influenza virus to bind to cell surfaces

Neuraminidase

This viral protein cleaves the glycosidic bonds to sialic acid residues which frees the virus to infect the host cell

Direct Viral Inhibition

This mechanism of anti-viral activity is described as collectins acting as neutralizing antibodies that inhibitt viral attachment and growth

Complement Activation

This mechanism of anti-viral activity is described as the binding of collectins to glycoproteins and glycolipids in the virion to activate the lectin and complement pathway

Opsonization

This mechanism of anti-viral activity is described as the binding of collectins to glycoproteins and glycolipids in the virion followed by endocytosis of the cells via a collectin receptor

Antibody Production → Stimulate immune response → Lectin Toxicity

This occurs when plant lectins aren’t cooked and aren’t digested properly

Phytohemagglutinin

Red kidney bean poisoning is attributed to what lectin?

P-selectin

This lectin allows for the rolling of neutrophils due to its binding of oligosaccharides and neutrophils at low affinity

Integrin

This substance stops the rolling of neutrophils and strengthens their adhesion which allows them to crawl into the tissue