Chromogranins from Cell Biology to Physiology and Biomedicine

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sequences (L42-L49; L57-L64). Surface interaction of rhodamine-labelled bCGA1-
40 was demonstrated using confocal microscopy after incubation of the labeled
peptide with A. fumigatus, A. brassicola and N. haematococca (Blois et al. 2006 ).
In addition, the interaction of bCGA1-40 with monolayers of phospholipids and
sterols, as models for the interaction with mammalian and fungal membranes was
investigated by the surface tension technique (Blois et al. 2006 ; Maget-Dana et al.
2002 ). These studies demonstrated that the N-terminal bCGA1-40 fragment inter-
acts with model membrane phospholipids in a manner consistent with an amphiphi-
lic penetration into membranes in a concentration range relevant for biological
activity in mammalian tissue (Blois et al. 2006 ).
When VS-I was treated with the protease Glu-C from S. aureus V8, one of the
generated peptide, chromofungin (CHR) (Lugardon et al. 2001 ), is the shortest active
VS-I-derived peptide with antimicrobial activities (Fig.  3 ). It is well conserved dur-
ing evolution (Fig. 4a) and displays antifungal activity at 2–15 μM against filamen-
tous fungi (N. crassa, A. fumigatus, A. brassicola, N. haematococca, F. culmorum, F.
oxysporum) and yeast cells (C. albicans, C. tropicalis, C. neoformans) (Lugardon
et al. 2001 ). Since this peptide was generated after digestion of the material present
in chromaffin secretory vesicles by the protease Glu-C from S. aureus, it may be
hypothesized that it is produced during infections by this pathogen. The 3-D struc-
ture of CHR has been determined in water-trifluoroethanol (50:50) by using^1 H-
NMR spectroscopy. This analysis revealed the amphipathic helical structure of the
sequence 53–56, whereas the segment 48–52 confers hydrophobic character

A

B

b CAT RSMRLSFRARGYGFRGPGLQL

h CAT S K A P

h P370L S K A L

h G364S S K A S P

p CAT K PA S

r CAT K A D P

m CAT K T A D

e CAT K A

f CAT KIPTKDQK E ASEE

344 364

b CGA LPVNSPMNKGDTEVMKCIVEVISDTLSKPSPMPVSKECFETLRGDERILSILRHQNLLKELQDLALQGAKERTHQQKK

hrVS-1 STA Q A

p CGA Q S

r CGA T K VL S P L Q V AQ QQ

m CGA T K VL S P L Q A PLK

o CGA TNN K N L IIE L I EI V N Q RR

e CGA DT V Q AP KH

f CGA SSLEGEDNTK N V ITQD L I E A M LQKAKK

1 78

Fig. 4 Sequence alignment of VS-I and CAT sequences of different species. (a) Sequence align-
ment of bovine CGA1–78 with hrVS-1 and corresponding fragments from several species. pCGA
(porcine, p), rCGA (rat, r), mCGA (mouse, m), oCGA (ostrich, o), eCGA (equine, e), fCGA (frog,
f). (b) Sequence alignment of bovine CGA344-364 with the corresponding fragments from several
species hCGA (human, h and mutations G364S, P370L), pCGA (porcine, p), rCGA (rat, r), mCGA
(mouse, m), eCGA (equine, e), fCGA (frog, f)

Involvement of Chromogranin A and Its Derived Peptides to Fight Infections