Chemistry Reference
In-Depth Information
26
Small Is Beautiful: Mini-Lectins in Host Defense
Robert I. Lehrer
Having already illustrated the emerging roles of glycans as biochemical signals in
fertilization, early embryogenesis and malignancy, we will next consider how some
antimicrobial peptides - an ancient means of host defense - interact with glycans.
Table 19.2 lists endogenous lectins that recognize foreign glycosignatures, among
them the defensins.
α
-Defensins, with 29-35 amino acid residues, and
θ
-defensins, with only 18 residues, are considerably smaller than hevein, a mini-
lectin found in plants, as described in Chapter 18 (see also Chapter 15 for defi ni-
tion). This chapter will focus on
- defensins - among the smallest known lectins
and the only cyclic peptides of animal origin. However, before you meet them, we
will introduce their older relatives.
θ
26.1
Meet the Families
The defensin peptides of vertebrate animals comprise three subfamilies, called
α
- ,
β
- and
θ
-defensins. The sequences of selected
α
- and
β
- defensin peptides appear
in Figure 26.1. Human
- defensin (
DEFA
) genes cluster on the short arm of
chromosome 8 (8p21), with many
α
- defensin (
DEFB
) genes located nearby. This
subtelomeric location favors gene reduplication, and several
DEFA
and
DEFB
genes show marked copy number polymorphism.
DEFA
genes encode pre-pro-
peptides containing a negatively charged pro-domain and positively charged
C-terminal defensin domain. After posttranslational processing, mature
β
α
- defen-
sin peptides have largely
-sheet structures that are stabilized by three intramo-
lecular disulfi de bonds. The
β
-defensins have similarly folded peptide
backbones, but show limited amino- acid identity.
Three of the six human
α
- and
β
- defensin peptides (HNP - 1 - 3) have identical sequences,
except for their N-terminal residue. Collectively, these three peptides comprise
5-7% of total protein of a human neutrophil [polymorphic neutrophils (PMNs)].
For any readers who are curious about the origin of the word ' neutrophil ' and its
abbreviation as 'PMN', both terms can be traced to the pioneering studies of Paul
α
