Manuscript to be reviewed Comprehensive classification of the plant non-specific lipid transfer protein superfamily towards its Sequence – Structure – Function analysis. Cecile Fleury 1 , Jerome Gracy 2 , Marie-Francoise Gautier 1 , Jean-Luc Pons 2 , Jean-Francois Dufayard 3 , Gilles Labesse 2 , Manuel Ruiz 3 , Frederic de Lamotte Corresp. 1 1 UMR AGAP, INRA, F-34060 Montpellier, France 2 CBS, CNRS Univ Montpellier INSERM, Montpellier, France 3 UMR AGAP, CIRAD, F-34398 Montpellier, France Corresponding Author: Frederic de Lamotte Email address:
[email protected] Background. Non-specific Lipid Transfer Proteins (nsLTPs) are widely distributed in the plant kingdom and constitute a superfamily of related proteins. More than 800 different sequences have been characterized so far, but their biological functions remain unclear. It has been clear for years that they present a certain interest for agronomic and nutritional issues. Deciphering their functions means collecting and analyzing a variety of data from gene sequence to protein structure, from cellular localization to the physiological role. As a huge and growing number of new protein sequences are available nowadays, extracting meaningful knowledge from sequence-structure-function relationships calls for the development of new tools and approaches. As nsLTPs show high evolutionary divergence, but a conserved common right-handed superhelix structural fold, and as they are involved in a large number of key roles in plant development and defense, they are a stimulating case study for validating such an approach. Methods. In this study, we comprehensively investigated 797 nsLTP protein sequences, including a phylogenetic analysis on canonical protein sequences, three-dimensional (3D) structure modeling and functional annotation using several well-established bioinformatics programs.