Cysteine-associated distribution of aromatic residues in disulfide-stabilized extracellular protein families

Stephen R. Campion, Jeffrey D. Longenberger, Melissa A. Sealie, H. Tina Guraya

Department of Science and Mathematics, Alvernia University, Reading, USA.

DOI: 10.4236/abc.2013.31012                

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.

Keywords

EGF; Sushi; Laminin; Immunoglobulin

Conflicts of Interest

The authors declare no conflicts of interest.

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