TITLE:
Cysteine-associated distribution of aromatic residues in disulfide-stabilized extracellular protein families
AUTHORS:
Stephen R. Campion, Jeffrey D. Longenberger, Melissa A. Sealie, H. Tina Guraya
KEYWORDS:
EGF; Sushi; Laminin; Immunoglobulin
JOURNAL NAME:
Advances in Biological Chemistry,
Vol.3 No.1,
February
26,
2013
ABSTRACT:
Cysteine-dependent protein sequences were downloaded
from annotated database resources to generate comprehensive EGF, Sushi,
Laminin and Immu- noglobulin (IgC) motif-specific sequence files. Each dataset
was vertically registered and the cumulative distribution of amino acid
functional group chemistry determined relative to the respective complement of
cysteine residues providing critical disulfide stabilization of these four
well-known modular motif families. The cysteine-aligned amino acid distribution
data revealed limited ionic, polar, hydrophobic or other side chain
preferences, unique to each protein scaffold. In contrast, all four
cysteine-dependent protein families exhibited strong positional preference for
the aromatic residues phenylalanine (Phe) and tyrosine (Tyr), relative to
analogous cysteine landmarks. More than eighty percent of the members in each
protein family were found to possesses the same conserved -Cys- (Xxx)3-4-(Phe/Tyr)-
arrangement, placing an aromatic amino acid at analogous EGF-C5+4,
Sushi-C2+4, Laminin-C7+4 and IgC-C1+5. Over seventy
percent of EGF, Sushi and IgC sequences exhibited a second obvious
Cys-associated aromatic site -(Phe/Tyr)-Xxx- Cysat EGF-C4-2,
Sushi-C2-2 and IgC-C2-2. The cysteine-associated
placement of aromatic amino acid chemistry in four major disulfide-dependent
protein families likely represents conservation of a molecular determinant of
global importance in the structure- function of this large and diverse subset
of extracellular proteins.