Protein Bioinformatics

Protein Bioinformatics

Project Leader:Vikram Alva
Department:Protein Evolution - Lupas
Assistant: Karin Lehmann
Phone:+49 7071 601-340
Fax:+49 7071 601-349
Staff:Alphabetical List | Alumni

Introduction

The total number of different proteins existing today is estimated to be a trillion. Although this may seem a vast number, the actual diversity of proteins in nature is rather limited. Many proteins share detectable similarity in sequence and structure, since they arose by amplification, recombination, and divergence from a basic complement of autonomously folding modules, referred to as domains. Indeed, sequence comparison of modern proteins shows that they fall into only about ten thousand domain families, which, based on structural similarity, can be grouped further into one of a thousand folds. Many of these folds were already established at the time of the Last Universal Common Ancestor, a theoretical primordial organism from which all life on earth descended.

We are broadly interested in understanding the events that led to the emergence of these first folds as well as the events that led to their diversification into the many functional protein families we recognize today. To track these events, we use sensitive sequence analysis tools to establish correlations between sequence and structure similarity of today’s proteins. Many of the tools we use are integrated into the MPI Bioinformatics Toolkit (http://toolkit.tuebingen.mpg.de), a one-stop, integrative resource for protein bioinformatic analysis, which we develop and maintain.

 

 

Selected Publications

Alva V, Lupas AN. Histones Predate the Split Between Bacteria and Archaea. Bioinformatics. 2018 Dec 6.

Alva V, Lupas AN. From ancestral peptides to designed proteins. Curr Opin Struct Biol. 2018 Feb;48:103-109.

Zimmermann L, Stephens A, Nam SZ, Rau D, Kübler J, Lozajic M, Gabler F, Söding J, Lupas AN, Alva V. A Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core. J Mol Biol. 2018 Jul 20;430(15):2237-2243.

Fuchs ACD, Alva V, Maldoner L, Albrecht R, Hartmann MD, Martin J. The Architecture of the Anbu Complex Reflects an Evolutionary Intermediate at the Origin of the Proteasome System. Structure. 2017 Jun 6;25(6):834-845.e5.

Lupas AN, Alva V. Ribosomal proteins as documents of the transition from unstructured (poly)peptides to folded proteins. J Struct Biol. 2017 May;198(2):74-81.

Alva V, Lupas AN. The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport. Biochim Biophys Acta. 2016 Aug;1861(8 Pt B):913-923.

Alva V, Söding J, Lupas AN. A vocabulary of ancient peptides at the origin of folded proteins. Elife. 2015 Dec 14;4:e09410.

Scharfenberg F, Serek-Heuberger J, Coles M, Hartmann MD, Habeck M, Martin J, Lupas AN, Alva V. Structure and evolution of N-domains in AAA metalloproteases. J Mol Biol. 2015 Feb 27;427(4):910-23.

Alva V, Remmert M, Biegert A, Lupas AN, Söding J. A galaxy of folds. Protein Sci. 2010 Jan;19(1):124-30.

Alva V, Koretke KK, Coles M, Lupas AN. Cradle-loop barrels and the concept of metafolds in protein classification by natural descent. Curr Opin Struct Biol. 2008 Jun;18(3):358-65.