Dresden 2017 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 20: Posters - Physics of the Genesis of Life (Focus Session)

BP 20.14: Poster

Dienstag, 21. März 2017, 14:00–16:00, P1A

Globular Protein Design from Ancestral Supersecondary Structures — •Mohammad ElGamacy, Murray Coles, and Andrei Lupas — Max Planck Institute for Developmental Biology, Tuebingen, Germany

Combinatorial reshuffling of subdomain-sized peptides may have provided a very economic means for sequence space navigation and thus protein fold evolution. Previously, through a bioinformatic study we identified a set of highly conserved, subdomain-sized motifs recurring across distant folds, a cue that such motifs may have predated the existing pedigree of folds. This has led to the hypothesis that these ancestral fragments may have provided the basic building blocks for modern protein folds. We also demonstrated repetition of these fragments as a mechanism in creating new folds. The aim of this work was to investigate an alternative mechanism via recombination of heterologous fragments, especially that we were unable to detect any such recombination incidents between the ancestral fragments in modern proteins. To provide an exemplar, we attempted to reconstruct a polymerase-beta N-terminal domain out of two conserved supersecondary structures derived from two unrelated folds. We have done so using a computational strategy that introduces a minimal number of mutations to the constituting fragments. The resulting NMR structure agreed with the designed coordinates with atomic accuracy, demonstrating that a recombination event and a few mutation are sufficient to evolve a new domain.