biostudies-literatureHao MSVetenskapsrådetSvenska Forskningsrådet FormasEnergimyndighetenVetenskapsrådet (Swedish Research Council)Energimyndigheten (Swedish Energy Agency)Svenska Forskningsrådet Formas (Swedish Research Council Formas)3429https://www.ebi.ac.uk/biostudies/studies/S-EPMC11039641biostudies-literatureUnknown15(1)Carbohydrate-binding modules (CBMs) are non-catalytic proteins found appended to carbohydrate-active enzymes. Soil and marine bacteria secrete such enzymes to scavenge nutrition, and they often use CBMs to improve reaction rates and retention of released sugars. Here we present a structural and functional analysis of the recently established CBM family 92. All proteins analysed bind preferentially to β-1,6-glucans. This contrasts with the diversity of predicted substrates among the enzymes attached to CBM92 domains. We present crystal structures for two proteins, and confirm by mutagenesis that tryptophan residues permit ligand binding at three distinct functional binding sites on each protein. Multivalent CBM families are uncommon, so the establishment and structural characterisation of CNature communicationsStructural and biochemical analysis of family 92 carbohydrate-binding modules uncovers multivalent binding to β-glucans.PMC110396412020-036182019-003892019-006926Li HKoskela SBulone VKvammen ANakajima MMcKee LSInman ARSaha SNakai HLarsbrink JHao MSTanaka NBranden GMazurkewich SfalseStructural and biochemical analysis of family 92 carbohydrate-binding modules uncovers multivalent binding to β-glucans.Carbohydrate-binding modules (CBMs) are non-catalytic proteins found appended to carbohydrate-active enzymes. Soil and marine bacteria secrete such enzymes to scavenge nutrition, and they often use CBMs to improve reaction rates and retention of released sugars. Here we present a structural and functional analysis of the recently established CBM family 92. All proteins analysed bind preferentially to β-1,6-glucans. This contrasts with the diversity of predicted substrates among the enzymes attached to CBM92 domains. We present crystal structures for two proteins, and confirm by mutagenesis that tryptophan residues permit ligand binding at three distinct functional binding sites on each protein. Multivalent CBM families are uncommon, so the establishment and structural characterisation of C2024-01-01T00:00:00Z2024 Apr2026-06-01T21:48:05.532Z2025-04-06T03:17:09.424ZS-EPMC110396413865376410.1038/s41467-024-47584-y