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Origins of Protein Functions In Cells
A. Pohorille, NASA-Ames Research Center
In modern organisms proteins perform a majority of cellular functions,
such as chemical catalysis, energy transduction and transport of material
across cell walls. Although great strides have been made towards
understanding protein evolution, a meaningful extrapolation from
contemporary proteins to their earliest ancestors is virtually impossible. In
an alternative approach, the origin of water-soluble proteins was probed
through the synthesis of very large libraries of random amino acid
sequences and subsequently subjecting them to in vitro evolution. This
novel approach revealed unique information about structural and
functional properties of primordial proteins. Evolution of the smallest
ATP-binding protein led to the identification of four families that have
amino acid sequences different from each other and dissimilar from those
of any known protein. This demonstrates that a single function might have
been carried out by several different, primordial proteins. The probability
of finding a functional protein among random sequences appears to be
similar to the probability of finding an RNA enzyme. Further optimization
of the structure and function of ATP-binding proteins and in vitro
evolution of a non-catalytic protein scaffold provided evidence that a small
number of mutations can yield dramatic improvements in protein
efficiency and lead to novel structures and functions. These are key
requirements for successful evolution and diversification of proteins.
Considerable progress has been also achieved in understanding the origins
of membrane proteins. Remarkably, despite overall complexity of these
proteins, their structural motifs are quite simple, with a-helices being most
common. Even though these motifs are not nearly as diverse as those of
water-soluble proteins, they are sufficiently flexible to adapt readily to the
functional demands arising during evolution. This conclusion is supported
by studies on simple synthetic models and natural proteins of non-genomic
origin, which do not require highly specific amino acid sequences. These
proteins possess properties that, at the first sight, appear to require
markedly larger complexity. (Supported by the NASA Exobiology
program and NASA Astrobiology Institute.)
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